Overdominant Model Research Articles

LncRNA MEG3, GAS5, and HOTTIP Polymorphisms Association with Risk of Polycystic Ovary Syndrome: A Case-Control Study and Computational Analyses.

As a multifactorial and endocrine disease, polycystic ovary syndrome (PCOS) affects approximately 5-20% of women worldwide. Recently, long noncoding RNAs (lncRNAs) have emerged as potent predictors of a particular phenotype in PCOS. Our preliminary study examines the link between polymorphisms in lncRNAs MEG3, HOTTIP, and GAS5 and the risk of PCOS. The present study included 200 women with PCOS and 200 healthy women. The studied variations were genotyped by applying the PCR-RFLP and the tetra-ARMS-PCR reaction) techniques. The effect of variation in lncRNA on miRNA:lncRNA interactions, lncRNA-RNA interaction network, and the impact of the variations on the splicing site were predicted using different computational databases. The codominant heterozygous (TC vs. TT) model, the dominant (TC + CC vs. TT) model, the overdominant (TT + CC vs. TC) model, the C allele of rs2023843, and the C allele of rs55829688 had a protective role against PCOS. The A allele of rs4081134 and G allele of rs7158663 of the MEG3 conferred an increased risk of PCOS by 1.37 and 1.44 folds, respectively. The interaction analysis revealed that TC/GG/AA/TC and TC/GG/GA/TC strongly decreased the risk of PCOS by 94 and 92%, respectively. Interestingly, MEG3 and HOTTIP variants can create or disrupt binding sites for several splicing factors. In our population, MEG3 rs4081134 and rs7158663, GAS5 rs55829688, and HOTTIP rs2023843 polymorphisms were associated with PCOS risk. Replication studies on larger sample sizes must be conducted to confirm these findings and investigate other potential causative factors involved in the pathophysiology of PCOS.

Polymorphic variants of the genes for enzymes of the antioxidant system, apoptosis and inflammation as potential predictors of myocardial infarction

Myocardial infarction (MI) is a multifactorial polygenic disease that develops as a result of a complex interaction of numerous genetic factors and the external environment. Accordingly, the contribution of each of them separately is usually not large and may significantly depend on the state of other accompanying factors. The purpose of the study was to search for informative predictors of MI risk based on polygenic analysis of polymorphic variants of (1) the antioxidant defense enzyme genes PON1 (rs662), PON2 (rs7493), CAT (rs1001179), MSRA (rs10098474) and GSTP1 (rs1695); (2) the apoptosis genes CASP8 (rs3834129), TP53 (rs1042522) and BCL2 (rs12454712); and (3) the inflammation genes CRP (rs1205), CX3CR1 (rs3732378), IL6 (rs1800795) and CCL2 (rs1024611). 591 DNA samples were used in the study (280 patients with the onset at 30 to 60 years, with an average age of 46.02 ± 6.17, and 311 control subjects aged 30 to 62, with an average age of 44.65 ± 7.07). All the participants were male and Tatars by ethnicity. The logistic regression analysis with various models demonstrated associations with MI of polymorphic variants of the genes CX3CR1 (rs3732378) (overdominant model – G/G + A/A vs A/G P = 0.0002, OR = 1.9), MSRA (rs10098474) (dominant model – T/T vs T/C + C/C P = 0.015, OR = 1.51), CCL2 (rs1024611) (recessive model – P = 0.0007 – A/A + A/G vs G/G OR = 2.63), BCL2 (rs12454712) (log-additive model – *C allele, P = 0.005, OR = 1.38). Using the Monte Carlo method and Markov chains (APSampler), combinations of alleles/ genotypes of the studied polymorphic loci associated with a high risk of MI were obtained, which, in addition to those identified during single-locus analysis, contained polymorphic variants of the genes CASP8, TP53, CAT, PON2, CRP, IL6, GSTP1. Among the combinations obtained, a pairwise analysis of possible non-linear interactions between the identified combinations of alleles/genotypes was carried out, which showed synergistic interactions of the polymorphic variants CX3CR1*A/G and CASP8*I/I, MSRA*C and CRP*C, CAT*C/T and MSRA*C, CAT*C/T and CX3CR1*A contributing to the development of MI. Based on the results obtained using multivariate logistic regression analysis, a predictive model was built to assess the risk of developing MI, the predictive ability of which reached the value AUC = 0.71 (AUC – area under the curve in ROC analysis).

Roles of the lncRNAs MEG3, PVT1 and H19 tagSNPs in gastric cancer susceptibility

BackgroundImproper expression of long noncoding RNAs (lncRNAs) can cause various cancers. Single nucleotide polymorphisms (SNPs) affect the expression and function of several key lncRNAs. We assessed the associations of MEG3, PVT1, and H19 lncRNA polymorphisms with susceptibility to gastric cancer (GC).MethodsIn Ardabil (a high-risk area in North‒West Iran), 795 blood samples were collected from 396 cases and 399 controls. The control subjects were randomly selected from individuals receiving regular physical examinations in this hospital with no self-reported cancer history and were frequency-matched to the case group by sex and 5-year age intervals. All the samples were genotyped via the Infinium HTS platform, which was subsequently followed by rigorous data quality control, as well as statistical and bioinformatic analyses.ResultsThe H19 rs2107425 SNP was associated with GC risk in a recessive model of inheritance (TT vs. CC + CT: OR = 1.87). The PVT1 rs13255292 variant in the overdominant model significantly reduced GC risk (CT vs. CC + TT: OR = 0.74). There was no significant association between H19 rs2839698, MEG3 rs116907618, or rs11160608, or PVT1 rs7017386, rs13254990 tagSNPs and susceptibility to GC. The interaction between H19 rs2107425 TT and PVT1 rs7017386 TC increased GC risk (OR = 3.73; pbon < 0.05). The MEG3, PVT1, and H19 variants were not associated with clinicopathologic characteristics.ConclusionsWe revealed significant associations of the H19 rs2107425 and PVT1 rs13255292 genetic variants with GC. Interestingly, the novel SNP‒SNP interaction of H19 and PVT1 tagSNPs had a greater effect than single SNP impacts did on GC risk, providing us with invaluable data to identify potential biological mechanisms involved in the development of GC.

The functional TNF-α-308G > a single-nucleotide polymorphism (rs1800629): association with the predictive indices of breast cancer carcinogenesis.

Compared with all other cancer types, Breast cancer (BC) among women has now exceeded them all as the primary reason for cancer worldwide. The BC represents 11.7% of all cancer cases and accounts for a predestined 2.3 million new cases. It is the fourth primary reason for cancer-associated deaths in women. With a staggering 200-400% increase in the relative incidence of BC in Egypt, there is an urgent need for new diagnostic or predictive markers. The current investigation aims to explore the connection of the functional TNF-α-308G > A (rs1800629) single-nucleotide polymorphism (SNP) with different breast cancer predictive indices. The ARMS-PCR method was used for genotyping TNF-α-308G > A SNP. Three groups were recruited for the study: 79 patients with benign breast inflammation (BBI); 163 with breast cancer (BC) and 144 controls (C). The TNF-α-308G > A SNP was distributed among different groups in a unique pattern; in the control group 63.9% of cases were in the GG, 34% were in the GA, and 2.1% were in the AA. The BC group had 14% GG, 79% GA, and 7% AA, while the BBI group had 24% GG, 76% GA, and 0% AA. The AA genotype and A allele represented a strong significant correlation with risk factors in the BC group (ORAA: 14.67 [95% CI = 3.78-56.91] and ORA: 0.27 [95% CI = 0.19-0.39], respectively; P < 0.0001) in contrast to the control group. However, in the BBI group, a strong significant correlation was noted with the GA genotype (ORGA: 5.93 [95% CI = 3.18-11.04] P < 0.0001). In the BC group, the AA genotype shows a significant increase in Nottingham Prognostic Index (NPI) in positive ER and PR in contrast to the relevant negative ones (P = 0.02 and 0.002, respectively). However, the GA genotype significantly increased NPI in positive Her2 and metastatic patients (P = 0.03 and 0.01, respectively). This research is the first to correlate TNF-α-308G > A (rs1800629) SNP in Egyptian BC patients. The A allele, GA & AA genotypes, and the Overdominant model of the TNF-α-308G > A gene variants were recorded as prognostic risk factors for BC carcinogenesis.

Association between genetic variants (rs2839698, and rs217727) in lncRNA H19 and Acute lymphoblastic leukemia susceptibility: a case-control study in the Iranian population

Leukemia is a cancer affecting the hematopoietic system with an unclear pathogenesis. Recent studies suggest a correlation between several long non-coding RNAs (lncRNAs) and leukemia development. This study focuses on the potential link between H19 (rs2839698 and rs217727) polymorphisms and Acute Lymphoblastic Leukemia (ALL) susceptibility. The study involved 150 patients with clinically confirmed ALL and 150 controls. This research included 150 Iranian patients, who were confirmed to have clinical ALL, and 150 healthy people as the control group. A kit was utilized to extract the DNA of all the samples. After preparing the samples, DNA genotyping was done by using the tetra-primer ARMS-PCR method. After adjusting for age using multivariate logistic regression analysis, individuals carrying the CT genotype of rs2839698 were found to have a significantly 0.32-fold reduced risk of ALL compared with carriers of the CC genotype. Furthermore, a significant 0.48-fold reduction in ALL risk was observed in patients with CT+TT genotype rs2839698 compared with CC. Moreover, the over-dominant model was applied to compare the CT genotype of rs2839698 with its CC+TT genotype, which showed a significant 0.36-fold reduction of ALL risk. Notably, the cases of ALL and the control group were not significantly different in terms of their genotype and allele frequencies of rs217727 polymorphism. Yet, the TT haplotype was significantly associated with ALL risk (OR: 1.64, p = 0.025). Following the findings of this study, it can be concluded that H19 SNP rs2839698, rather than rs217727, might act as an innovative susceptibility marker for ALL leukemia.

Association between human telomerase reverse transcriptase (hTERT) MNS16A polymorphism and risk of breast cancer.

It is well known that telomerase activity is suppressed in normal human tissues and reactivated in tumors, suggesting that the human telomerase reverse transcriptase (hTERT, MIM: 187270) gene may be involved in carcinogenesis. A polymorphic tandem repeat minisatellite located downstream of exon 16 of hTERT and upstream in the putative promoter region of an antisense hTERT transcript, termed MNS16A, results in a functional polymorphism. Because the association between the MNS16A genetic polymorphism and breast cancer (BC) risk remains an open question, the present case-control study was conducted in Shiraz (Fars Province, Southern Iran). A total of 711 samples were collected, including 362 BC patients and 349 healthy individuals. Genotyping was performed by polymerase chain reaction method. Alleles were determined by classifying DNA amplicons of less than and greater than 300bp as short (S) and long (L) alleles, respectively. Different inheritance models (codominant, dominant, recessive, overdominant genotype models and the allele model) were used to evaluate the association between the MNS16A polymorphism and the risk of BC. No significant association was observed in any of the analyses. It should be noted that the statistical power of the comparisons was low. The present study did not support the association between hTERT MNS16A polymorphism and breast cancer risk. Similar studies in other populations with larger sample sizes are needed to determine the association between the hTERT MNS16A polymorphism and susceptibility to breast cancer.

Polymorphism Of Orosomucoid-Like 3 ORMDL3 Rs4795405 C&gt;T In Iraqi Patients with Asthma

The aim of this study was to investigate the association of polymorphism of Orosomucoid-like 3 ORMDL3 rs4795405 C/T gene to the susceptibility of asthma among Iraqi asthmatic patients. Forty-five asthmatic patients (23 males and 22 females), their age 19-70 years and 35 healthy controls( 18 males and 17 females) ,their age 18-71years were selected from Wasit Province using a convenient sampling method. Genetic polymorphism of Orosomucoid-like 3 ORMDL3 rs4795405 C&gt;T was carried out using TaqMan -PCR. both patients and control groups, the distribution frequencies of genotypes and alleles of the rs4795405 C/T gene were in Hardy-Weinberg equilibrium (P&lt;0.05) .The most common genotype in both control and asthma patients was the heterozygous genotype CT with a percentage of 67% and 66% respectively. The genotype CC was higher in the asthmatic group (20%) compared to the control group (14%). In contrast, genotype TT, the less predominant genotype, was less in the asthmatic group were less in asthmatic group (13%) compared control group (20%).The C allele was more frequent in asthma patients than in healthy controls (53.33%vs47.14%), whereas the T allele was frequent in healthy controls than in asthma patients (52.86% vs 46.67%) with no significant differences. The association analysis displayed that the individuals carrying the homozygous CC genotype were more likely to have a increased risk of asthma with OR=1.5(CI95% 0.4537to4.9593) ,P=0.5063.The heterozygous genotypes CT was not associated with asthma with OR=1.0 (CI95%0.4103 to2.6538 ),P=0.9288 . The TT genotype decreases the association with asthma OR=0.6 (CI950.1865 to2.0302), P =0.4253. These results suggested that the T allele might play a protective role against asthma whereas the C allele might consider a risk factor in asthma. The subgroup analysis revealed that the asthma risk of females with ORMDL3 CC genotype was 2.4 fold increases the risk of asthma OR=2.4889 (CI95% 0.5478to11.3081), P= 0.2377 The TC and TT genotype decreases the association with the disease with with OR = 0.8485 (CI 95% 0.2312to3.1142), P = 0.8044 and OR= 0.2121(CI95% 0.02 to2.2473)P =0.1979 respectively. Among males, ORMDL3 CT genotype ncreased asthmatic risk among patients’ males 1.3 fold, OR= 1.3333 (CI95%0.3433 to 5.1781), P=0.6777. The genotype CC decreases the association with the disease OR=0.3810 (CI95%0.0317to 4.5813), P=0.4469. While, the homozygous TT genotype was not associated with the disease OR=1.0294 (CI95% 0,2313 to4.5814), P=0.9696. The analysis of genetic model for Orosomucoid-lik 3 ORMDL3 rs4795405 showed the recessive model (CC+CT/ TT ) increased the association with the asthma OR=1.6250 P=0.4253.The Over-dominant model(CT+TT/ CC) and the dominant model(CT+TT/ CC) decreased the association with asthma OR=0.9583,P=0.9288and OR= 0.6667 ,P=0.5063 respectively.

Polymorphism of 8-oxoguanine DNA glycosylase -1(OGG1)in Iraqi Patients with Type2 Diabetes Mellitus

Chronic hyperglycemia in type 2 diabetes mellitus leads to elevated oxidative stress. As a consequence , the accumulation of reactive oxygen species (ROS)may cause additional damage to various biological macromolecules, including DNA. Several studies have demonstrated that oxidative stress plays an important role in the pathogenesis of type2 diabetes mellitus. The aim of this study is to investigate the association of polymorphisms of 8- oxoguanine DNA glycosylase-1(OGG1) repair gene polymorphism to the susceptibility of type 2 DM in an Iraqi population with T2DM patients from Wasit Province. All samples were collected from the local community of Wasit province, Iraq. Forty five type 2 diabetes mellitus patients (22 males and 23 females) and 35 healthy controls (17 males and 18 females) were genotyped for 8-oxoguanine DNA glycosylase-1(OGG1) using PCR- RFLP technique. In both patients and control groups, the distribution frequencies of genotypes and alleles of 8-oxoguanine DNA glycosylase-1(OGG1) A/G was inconsistent with the Hardy-Weinberg equilibrium in T2DM patients(χ2=49.542,P=(0.00001); χ2=82.0185,P=(0.0001) respectively. The Cys/Cys(mt/mt) OGG1 genotype was significantly higher in patients than controls(mt/mt;33(37%)vs,0.00 in controls. The Ser/Cys (wt/mt) was 7(16%) and 6(17%) in patients and controls respectively and Ser/Ser genotypes wt/wt; decreased significantly in patients 5(11%) vs,29(83%) in controls. The wt and mt allele frequencies of OGG1were highly significant between the two groups P=0.00001. The wt allele was the major one in control group with a percent of (90.28) vs. (18.89) in patients group. Whereas the mt the frequent allele in patients with a percent of (81.11) vs. (18.89).This further analysis showed that the individuals carrying the homozygous Cys/Cys(mt/mt) genotype were more likely to have increased the risk of T2DM very significantly with OR= 190.02800 (CI95% 10.8329 to 3342.2603) ,P=0.0003. The genotypes Ser/Ser( wt/wt) and Ser/Cys(wt/mt) decrease the association with T2DM with OR=0.0259 (CI95% 0.0072 to 0.0930), and 0.8904 (CI95% 0.2701 to 2.9347 )respectively, P= 0.0001 and 0.08486 for each genotype respectively, These results suggest that mt allele may be considered as risk allele of T2DM whereas the wt allele is protective agent T2DM.Association analysis showed that the type2 diabetes mellitus risk of females with OGG1 gene Cys/Cys( mt/mt) genotype was highly significant 81.4000 fold higher than that in controls OR= 81.4000 (CI 95% 4.3089 to 1537.7322), P= 0.0033.Ser/Cys( wt/mt) genotype increase the probability of the disease with OR = 1.7647 (CI 95% 0.3745 to 8.3154), P = 0.4727.Similary,Ser/Ser(wt/wt) genotype decrease the association with T2DM with OR= 0.0091 (CI95% 0.0009 to 0.0959), P = 0.0001.Type2 diabetes mellitus patients particularly with Cys/Cys(mt/mt) genotype increases the association about more than 111 times in males patients than that in controls OR= 111.3636 ( CI95% 5.7135 to2170.6226), P = 0.0019 While, genotypes Ser/Cys(wt/mt) and Ser/Ser (wt/wt) reduce the likelihood of T2DM with OR= 0.2222 ( CI95% 0.0209 to 2.3585),P = 0.2120 and 0.0476( CI95% 0.0091 to 0.2484), P= 0.0003 respectively. the genetic model for OGG1 in comparison between T2DM patients and controls . The dominant model indicated that patients and controls of (wt/mt+mt/mt) genotype increased significantly the association with T2DM in patients: (5/7 and 33) comparing with control (29/6 and 0.00) with OR (38.666),P=0.0001.The recessive model revealed that patients carrier the genotype (wt/wt+wt/mt) declined significantly the association with the disease :(33/5 and 7) in patients versus (0.00/29 and 6) in controls,OR=0.0053,P=0.0003.The Over-dominant model showed that patients with the genotype (wt/wt+mt/mt) in creased non-significantly the association with the disease when compare patients (7/5 and 33) with controls(6/29 and 0.00) ,OR=1.123,P=0.848

Association of RIPK1 and RIPK2 Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Han Population.

Rheumatoid arthritis (RA) is a systemic autoimmune disease with an obscure pathogenesis. This study aims to identify the susceptibility conferred by specific single nucleotide polymorphisms (SNPs), namely rs17548629 within the RIPK1 gene and rs10094579 within the RIPK2 gene, in RA. Additionally, it investigates the associations between inflammatory markers and biochemical parameters at various stages of the disease. We analyzed 394 patients with RA and 258 normal controls (NCs), examining SNPs within the RIPK1 (rs17548629) and RIPK2 (rs10094579) genes using polymerase chain reaction (PCR) and sequencing techniques. Profiles of RA patients were evaluated for inflammatory markers, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), as well as biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, glucose, uric acid, and creatinine. Additionally, disease-specific indicators included cyclic citrullinated peptide (CCP), rheumatoid factor (RF), antinuclear antibodies (ANA), and anti-keratin antibodies. The Disease Activity Score 28 (DAS28), based on ESR, was used to categorize RA patients into groups of high, moderate, or low disease activity. We found a significant association between the RIPK1 rs17548629 genotype and RA in the additive model (p < 0.001; OR = 3.23), over-dominant model (p < 0.001; OR = 0.27), and dominant model (p < 0.001; OR = 3.94). The frequency of the C allele at rs17548629 was significantly higher in NCs than in RA patients (p < 0.001; OR = 0.322). When compared with normal controls, the RIPK1 rs17548629 genotype demonstrated significant associations with both anti-CCP-positive RA patients (p < 0.001) and anti-CCP-negative RA patients (p < 0.001). Similarly, this genotype was associated with RF-positive RA patients (p < 0.001). Furthermore, the RIPK2 rs10094579 genotype was significantly associated with CRP levels in RA patients with low disease activity in the over-dominant model (p = 0.029; OR = 0.065, adjusted for age and sex). The presence of the RIPK1 rs17548629 genotype is associated with RA under additive, co-dominant, and dominant models. The T allele mutation at rs17548629 increases the risk of RA in the Chinese population. The RIPK1 rs17548629 genotype was identified as being associated with RF-positive RA patients, whereas no significant association was observed in RF-negative individuals. These findings suggest that this SNP may modulate the risk of RA in an RF-dependent manner. Furthermore, the RIPK2 rs10094579 genotype correlates with CRP levels in RA patients exhibiting low disease activity. This association underscores the necessity for caution when reducing the dosage of therapy in RA patients with low disease activity who carry the CA genotype at RIPK2 rs10094579. Additional research is warranted to explore other genotypes that may influence RA susceptibility and to refine potential treatment strategies.

Https://publishing.emanresearch.org/Journal/Abstract/angiotherapy-81010000

Background: The global prevalence of type 2 diabetes mellitus (T2DM) is projected to rise significantly, with an estimated increase from 536.6 million cases in 2021 to 783.2 million by 2045. Genetic predisposition plays a crucial role in T2DM susceptibility, with the FTO gene, particularly the single nucleotide polymorphism (SNP) rs11076023, being linked to the disease. Methods: A comprehensive literature search was conducted using PubMed, Scopus, and Google Scholar to identify relevant studies that examined the association between the FTO gene rs11076023 polymorphism and T2DM. Case-control studies published until December 31, 2023, were included, adhering to PRISMA guidelines. Data extraction was performed systematically, and statistical analysis was conducted using MetaGenyo to assess the association across various genetic models. Results: The meta-analysis encompassed three studies involving 3,887 participants (1,985 cases and 1,902 controls). The findings demonstrated a significant association between the T allele of rs11076023 and increased T2DM risk, particularly within the recessive genetic model (TT vs. TA + AA), indicating a higher susceptibility among individuals with the TT genotype. In contrast, the over-dominant model suggested a protective effect associated with the TA heterozygous genotype. Notable heterogeneity was observed across the studies, and sensitivity analyses confirmed the robustness of the associations. Conclusion: This meta-analysis highlights the FTO gene rs11076023 polymorphism as a significant genetic factor influencing T2DM susceptibility, particularly within certain population subsets. The findings underscore the complexity of T2DM risk, emphasizing the interplay between genetic factors and lifestyle choices. Further research with larger, diverse populations is necessary to validate these associations and explore the underlying biological mechanisms, which may inform targeted interventions for T2DM prevention and management.

Association of OAS1 and MxA variants with COVID-19 in Pakistani patients.

Coronaviruses, a family of enveloped RNA viruses, have been implicated in various clinical disorders including coronavirus disease 2019 (COVID-19). Host genetic factors, including the OAS1 and MxA gene variants may have a role in determining susceptibility to viral infections. Understanding the genetic factors involved in unraveling COVID-19`s diverse clinical outcomes is critical for disease management. This study investigated the impact of OAS1 rs2660 and MxA rs2071430 genotypes on COVID-19 susceptibility and severity among Pakistani patients. This was a comparative cross-sectional study. Fifty patients diagnosed with COVID-19 and 50 controls were recruited and genotyped for the selected gene variants. The OAS1 gene rs2660 exhibited an association with COVID-19 susceptibility in various genetic models. The risk decreased with AG genotype (OR = 0.23, 95% CI = 0.09-0.58; p = 0.0011) compared to GG in codominant models. In dominant (OR = 0.35, 95% CI = 0.15-0.81; p = 0.013) and overdominant (OR = 0.21, 95% CI = 0.08-0.53; p = 0.0005) models, the single nucleotide variant (SNV) decreased COVID-19 susceptibility risk. There was no association of OAS1 rs2660 genotypes with COVID-19 severity. We did not find a significant association between MxA rs2071430 variant and COVID-19 susceptibility. OAS1 rs2660 AG genotype showed decreased risk of COVID-19 susceptibility among Pakistani patients. This study provides insight into the role of the OAS1 and MxA variants in COVID-19. This finding could aid researchers in understanding genetic susceptibility and severity in COVID-19 by identifying at-risk individuals and determining the optimal treatment.

Association of β1- and β2-Adrenergic Receptor Gene Polymorphisms with the Effectiveness of Bisoprolol and Carvedilol in Patients with Heart Failure of Ischemic Etiology

The aim. To study the relationship between β1-, β2-adrenergic receptor (β-AR) gene polymorphisms and the effectiveness of bisoprolol and carvedilol in patients with heart failure (HF) and coronary heart disease. Materials and methods. We examined 201 patients with HF on the background of post-infarction cardiosclerosis. Control group included 43 healthy individuals of comparable age and sex. Genotyping was carried out for 3 polymorphisms (rs1801253 and rs1801252 of the β1-AR gene; rs1042714 of the β2-AR gene). The patients were divided into 2 groups: the first group included 104 (51.7%) patients who took bisoprolol during the year of observation; 97 (48.3%) patients of the second group were treated with carvedilol. Statistical analysis was performed using Statistica 10.0 and SNPStats programs. Results. In patients with HF, the mutant C-allele (rs1801253 polymorphism) of the β1-AR gene was associated with a decrease in the probability of heart rate reduction &gt;15 min-1 against the background of the use of β-blocker during the year (odds ratio [OR] = 0.42 [0.16-0.98], p = 0.041, recessive inheritance model; OR = 0.62 [0.40-0.97], p = 0.038; log-additive inheritance model). The probability of positive dynamics of the left ventricular ejection fraction (LVEF) increased in carriers of the wild A-allele of the rs1801252 (Ser49Gly) polymorphism of the β1-AR gene (OR = 4.86 [2.35-10.08], p &lt; 0.0001, codominant model; OR = 5.18 [2.51-10.68], p &lt; 0.0001, dominant model; OR = 4.68 [2.26-9.68], p &lt; 0.0001, over-dominant model; OR = 5.05 [2.48-10.28], p &lt; 0.0001, log-additive inheritance model). The probability of an increase in LVEF within a year increased with treatment with carvedilol in homozygous mutant G/G rs1042714 polymorphism (Gln27Glu) of the β2-AR gene in patients with HF (OR = 6.09 [1.16-31.88], p = 0.038, dominant inheritance model). Conclusions. Patients with HF of ischemic etiology, carriers of the mutant C-allele of rs1801253 polymorphism of the β1-adrenoceptor gene, are worse responders to the use of β-blockers compared to patients with the wild G-allele (a lower proportion of patients with a decrease in heart rate &gt;15 min-1: 6.8% vs. 14.5%, respectively; OR = 0.42 [0.16-0.98], p = 0.041). The frequency of an increase in the value of the LVEF &gt;10% was higher compared to patients with the mutant G-allele (39.3% vs. 11.1%, respectively; OR = 4.86 [2.35-10.08], p &lt; 0.0001) against the background of application of β-blockers. The use of carvedilol was more appropriate in homozygous carriers of the mutant G-allele of the rs1042714 polymorphism (Gln27Glu) of the β2-AR gene compared to bisoprolol (a greater proportion of patients with an increase in the LVEF: 17.6% vs. 9.1%, respectively; OR = 6.09 [1.16-31.88], p = 0.038). No probable associations of rs1801253 and rs1801252 polymorphisms of the β1-AR gene with the pharmacodynamics of bisoprolol and carvedilol in patients with HF of ischemic etiology were found.

Association of the Single Nucleotide Polymorphisms rs11556218, rs4778889, rs4072111, and rs1131445 of the Interleukin-16 Gene with Ovarian Cancer.

Single nucleotide polymorphisms (SNPs) of the IL-16 gene have been reported to influence the risk of several cancers, but their role in ovarian cancer (OC) has not been studied. Using the restriction fragment length polymorphism (PCR-RFLP) method, we examined four IL-16 SNPs: rs11556218 (T > G), rs4778889 (T > C), rs4072111 (C > T), and rs1131445 (T > C) in blood samples from 413 women of Central European descent, including 200 OC patients and 213 healthy controls. Among the patients, 62% were postmenopausal, 84.5% were diagnosed in late stages (FIGO IIb-IV), and 73.5% had high-grade serous OC (HGSOC). Minor allele frequencies in controls were 9.2% for rs11556218 (G allele), 13.7% for rs4778889 (C allele), 10.4% for rs4072111 (T allele), and 32.3% for rs1131445 (C allele). We found significant associations of rs11556218 (G vs. T allele: OR 2.76, 95% CI 1.84-4.14, p < 0.0001) with elevated OC risk in the whole cohort (p < 0.001) and in both premenopausal (p < 0.001) and postmenopausal (p = 0.001) subgroups. These associations remained significant across heterozygote (p < 0.001), dominant (p < 0.001), and overdominant (p < 0.001) models. IL-16 rs4778889 was associated with OC risk predominantly in premenopausal women (p < 0.0001 in almost all models). In the whole cohort, the C allele was associated with OC risk (OR 1.54, CI 95% 1.06-2.23, p = 0.024), and the association of rs4778889 was significant in dominant (p = 0.019), overdominant (p = 0.033), and heterozygote (p = 0.027) models. Furthermore, rs4778889 was linked with HGSOC (p = 0.036) and endometriosis-related OC subtypes (p = 0.002). No significant associations were found for rs4072111 or rs1131445 (p = 0.81 or 0.47, respectively). In conclusion, rs11556218 and rs4778889 SNPs are associated with OC risk, especially in premenopausal women.

ASSOCIATION OF GROWTH HORMONE RECEPTOR (GHR) GENE POLYMORPHISMS WITH BODY WEIGHT OF RABBITS: A SYSTEMATIC REVIEW AND META-ANALYSIS

The growth hormone receptor (GHR) gene plays a key role in regulating growth and metabolism. However, the relationship between polymorphic variants of this gene and the body weight of rabbits under different genetic models has not been established. Thus, the objective of this study was to evaluate relationship between GHR gene polymorphisms and body weight of rabbits. Relevant literatures were systematically reviewed using the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guideline. 248 studies were identified and screened against pre-determined inclusion criteria and data were extracted from 17 studies. Each study was subjected to Hardy-Weinberg Equilibrium (HWE) test and six genetic models consisting of co-dominant, dominant, recessive and over-dominant models were fitted using OpenMeta® Analyst Software. The Cohen’s d method was used to calculate standardized mean differences (SMDs) to estimate individual study effect size as well as the overall effect size. Heterogeneity measures were inferred from the Q statistic (based on Chi-square test) and its associated p-value, Tau-squared (τ2), H-squared (H2) and I-squared (I2) values. Publication bias was assessed by Egger’s regression asymmetry test and sensitivity analysis was conducted to detect if the overall effect size was largely due to a single study effect size. There was significant association (P&lt;0.05) of GHR gene with body weight of rabbits under one of the co-dominant models (CG vs GG). However, this association was not significant (P&gt;0.05) under all other genetic models. Further, the results indicated that, cumulatively for all studies included in the meta-analysis of association of GHR gene with body weight of rabbits, GG genotype had higher body weight than CG genotype. However, there was no difference (P&gt;0.05) between CC and CG and CC and GG genotypes. These findings implied that the impact of GHR gene polymorphisms on body weight in rabbits may be influenced by specific genetic models.

Neural EGFL like 1 as a novel gene for Trabecular Bone Score in older adults: The Bushehr Elderly Health (BEH) program.

Neural EGFL like 1 (NELL-1), is a secreted glycoprotein and stimulates osteogenic cell differentiation and bone mineralization. This study aimed to explore the relationship between NELL-1 and Trabecular Bone Score (TBS) as a novel tool for the evaluation of osteoporosis in an elderly population-based cohort study in Iran. A single-locus analysis was performed on TBS using data from 2,071 participants in the Bushehr Elderly Health (BEH) Program. The study investigated 376 independent single nucleotide polymorphisms (SNPs) within the NELL-1 on chromosome 11p15.1. The association between SNPs and the mean TBS L1 to L4 was analyzed through an additive model. Significant variants in the additive model (PFDR<0.05) were further examined within dominant, recessive, over-dominant, and co-dominant models. Multiple linear regression was employed to assess the relationship between the genetic risk score (GRS) derived from significant SNPs and TBS. Three SNPs within the NELL-1 showed a statistically significant association with TBS after adjusting for age and sex. The associations for rs1901945 (β = 0.013, PFDR = 0.0007), rs1584851 (β = -0.011, PFDR = 0.0003), and rs58028601 (β = 0.011, PFDR = 0.0003) were significant in the additive model. Additionally, significant results were observed for rs1901945 and rs58028601 in the dominant model (P<0.05). The GRS showed a statistically significant relationship with TBS, considering adjustments for age, sex, Body Mass Index, type 2 diabetes, and smoking (β = 0.077, P = 1.7×10-5). This study highlights the association of NELL-1 with TBS, underscoring its potential as a candidate for further research and personalized medicine concerning the impact of this gene on bone quality.

The rs3918188 and rs1799983 loci of eNOS gene are associated with susceptibility in patients with systemic lupus erythematosus in Northeast China

To investigate the association between single nucleotide polymorphism (SNP) at the rs3918188, rs1799983 and rs1007311 loci of the endothelial nitric oxide synthase (eNOS) gene and genetic susceptibility to systemic lupus erythematosus (SLE) in northeastern China. The base distribution of eNOS gene rs3918188, rs1799983 and rs1007311 in 1712 human peripheral blood samples from Northeast China was detected by SNaPshot sequencing technology. The correlation between genotype, allele and gene model of these loci of the eNOS gene and the genetic susceptibility to SLE was investigated by logistic regression analysis. The results of the differences in the frequency distribution of their gene models were visualised using R 4.3.2 software. Finally, HaploView 4.2 software was used to analyse the relationship between the haplotypes of the three loci mentioned above and the genetic susceptibility to SLE. A multifactor dimensionality reduction (MDR) analysis was used to determine the best SNP-SNP interaction model. The CC genotype and C allele at the rs3918188 locus may be a risk factor for SLE (CC vs AA: OR = 1.827, P < 0.05; C vs A: OR = 1.558, P < 0.001), and this locus increased the risk of SLE in the dominant model and the recessive model (AC + CC vs AA: OR = 1.542, P < 0.05; CC vs AA + AC: OR = 1.707, P < 0.001), while the risk of SLE was reduced in the overdominant model (AC vs AA + CC: OR = 0.628, P < 0.001). The GT genotype and T allele at locus rs1799983 may be a protective factor for SLE (GT vs GG: OR = 0.328, P < 0.001; T vs G: OR = 0.438, P < 0.001) and this locus reduced the risk of SLE in the overdominant model (GT vs GG + TT: OR = 0.385, P < 0.001). There is a strong linkage disequilibrium between the rs1007311 and rs1799983 loci of the eNOS gene. Among them, the formed haplotype AG increased the risk of SLE compared to GG. AT and GT decreased the risk of SLE compared to GG. In this study, the eNOS gene rs3918188 and rs1799983 loci were found to be associated with susceptibility to SLE. This helps to deeply explore the mechanism of eNOS gene and genetic susceptibility to SLE. It provides a certain research basis for the subsequent exploration of the molecular mechanism of these loci and SLE, as well as the early diagnosis, treatment and prognosis of SLE.

Exploring the Role of the TAS2R16 Protein and Its Single Nucleotide Variants in Pituitary Adenoma Development.

Pituitary adenoma (PA) is a common benign tumor that develops in the pituitary gland, causing hormonal imbalances and potential health issues. The TAS2R16 gene codes for a taste receptor and is involved in bitter taste perception, but there is currently no known direct link between this gene and pituitary adenoma. This study included 221 healthy controls and 131 patients with pituitary adenoma (PA) from the Lithuanian population. DNA was isolated from peripheral venous blood using the salt precipitation method. Genotyping was performed via RT-PCR. Statistical analysis was conducted with IBM SPSS Statistics 29.0 software, incorporating the Bonferroni correction for multiple comparisons. This study found that the TAS2R16 rs978739 C allele is less common in the non-invasive PA group compared to the control group (p = 0.045). The TAS2R16 rs860170 CT genotype reduces the likelihood of developing non-invasive PA by 1.9-fold under the codominant (p = 0.024) and overdominant (p = 0.030) models. The odds of developing non-invasive PA are reduced by 2-fold under the dominant (p = 0.021) model for TAS2R16 rs860170 CT + CC genotypes and by 2-fold under the additive (p = 0.018) model for each TAS2R16 rs860170 C allele. The PA group had higher serum levels of TAS2R16 than the control group (p < 0.001). The present study found that patients with the TAS2R16 rs978739 TT or CT genotype had higher serum TAS2R16 levels and protein concentrations than healthy individuals (p = 0.025 and p = 0.019, respectively), and those with the AA or AG genotype of TAS2R16 rs1357949 had higher protein concentrations (p = 0.005 and p = 0.007, respectively). The TAS2R16 rs978739 C allele was less common in the non-invasive PA group compared to the control group, while the TAS2R16 rs860170 CT genotype was linked to a reduced likelihood of developing non-invasive PA. Additionally, the PA group showed higher serum levels of TAS2R16, and increased serum protein concentrations were observed in PA patients with specific TAS2R16 variants.

CXCL12 Gene Polymorphisms and Serum Levels: Associations with Multiple Sclerosis Prevalence and Clinical Parameters in Lithuania.

Our study aimed to investigate the associations between CXCL12 rs1029153, rs1801157, and rs2297630 single-nucleotide polymorphisms (SNPs), CXCL12 protein levels, MS prevalence, and clinical parameters. This study included 250 individuals diagnosed with MS and 250 sex- and age-matched healthy control individuals from Lithuania. The SNPs were genotyped with real-time PCR-based assays. The CXCL12 protein concentration was evaluated in serum using the ELISA method. Of the studied CXCL12 SNPs, we found that the rs1801157 CT genotype in the males was associated with 2.3 times reduced MS odds when compared with the CC genotype according to the overdominant and codominant models (p = 0.011 and p = 0.012, respectively). There was a tendency, which did not reach adjusted statistical significance, for a lower CXCL12 protein concentration in the healthy individuals with the rs1801157 CT genotype (p = 0.028). Sensory symptoms were rarer in the women with the rs1801157 TT genotype (p = 0.004); however, this genotype was also associated with a shorter MS disease duration (p = 0.007). CXCL12 rs1801157 was associated with reduced odds of MS occurrence in the male individuals. In women, rs1801157 was associated with a sensory symptom prevalence.

Association of candidate gene (INSR & THADA) polymorphism with polycystic ovary syndrome: meta-analysis and statistical power analysis.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that impacts women before reaching menopause. In addition to notable features (irregular ovulation, elevated androgen levels, and the existence of numerous ovarian cysts), individuals with PCOS frequently encounter diverse metabolic, cardiovascular, and psychological conditions. The onset of PCOS is influenced by a combination of factors, and various genetic variations are believed to play a significant role in its progression. The objective of the current study was to explore the link between genetic variations in the candidate genes thyroid-adenoma-associated (THADA) gene and insulin receptor (INSR) and susceptibility to developing PCOS. We conducted an extensive search across various databases, including Google Scholar, PubMed, Science Direct, Scopus, and EMBASE, to compile relevant case-control studies and literature reviews for subsequent statistical analysis. In the present study, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was followed, a guideline for Systematic Reviews and Meta-Analysis. While a previous meta-analysis explored the correlation between INSR rs1799817 and THADA rs13429458 and their association with susceptibility to PCOS, our current study did not integrate any findings from these prior investigations. Our research encompassed articles published between 2017 and 2023, and we employed MetaGenyo software to assess the collected data. Statistical power analysis was performed using G*Power 3.1 software. Odds ratios and their corresponding 95% confidence intervals were calculated for each genetic model. Fifteen studies that met the criteria were analyzed. Out of these, ten studies, involving 1,189 cases and 1,005 controls, examined the INSR rs1799817 gene polymorphism, while five studies, including 783 cases and 553 controls, investigated the THADA rs13429458 gene polymorphism. The meta-analysis results indicated that there was no statistically significant association between the INSR rs1799817 gene polymorphism and the risk of PCOS (p>0.05). In contrast, the THADA rs13429458 gene polymorphism showed a significant association with PCOS risk under the over-dominant model (p<0.05). The present meta-analysis demonstrated a notable association between the THADA rs13429458 gene polymorphism and the likelihood of developing PCOS. Further rigorous studies with expanded sample sizes and diverse ethnic representation will be important to comprehensively evaluate and validate these findings.

Association of a NLRP3 rs10754558 Polymorphism with the Development of Chronic Helicobacter pylori Infection in South Indian Tamils

The increased prevalence of Helicobacter pylori infection and inadequate genetic research on the same, demands a genetic study among Tamil population of South India to unravel the association of NLRP3 (NLR family pyrin domain containing 3) variants with persistent H. pylori infection. This research was aimed to study the correlation between persistent H. pylori infection and influence of such genetic variants in the development of disease progression. In this study, 200 healthy volunteers and 120 H. pylori-positive cases were screened for two NLRP3 variants, rs74163773 and rs10754558, using allele-specific PCR and TaqManTM SNP genotyping assay, respectively. Based on our genotype and allelic distribution, rs74163773 variant did not associate with the risk of developing the persistent infection. However, a significant association of heterozygous CG variant of rs10754558 with patient showing clinical symptoms of gastritis, PUD and persistent infection in the over-dominant, co-dominant and recessive models was found. Our findings suggest that persistent H. pylori infection susceptibility was influenced by genetic variant rs10754558 and its heterozygous CG variant can serve as an independent risk factor in the manifestation of chronic gastritis and PUD in the South Indian Tamils.