CC Genotype Research Articles

MiR-146a (rs2910164) Gene Polymorphism and Its Impact on Circulating MiR-146a Levels in Patients with Inflammatory Bowel Diseases.

MicroRNA-146a (miR-146a) has been involved in the pathophysiology of inflammatory bowel disease (IBD). However, the precise processes are still not entirely understood. Contradictory studies suggest that miR-146a expression could be influenced by the miR-146a rs2910164 C > G polymorphism. This case-control study aimed to investigate the association ofmiR-146a rs2910164 C > G gene polymorphism and its impact on circulating miR-146a expression levels in Egyptian IBD patients. We included 40 IBD patients and 30 matched healthy controls. Genotyping of miR-146a rs2910164 polymorphism and assessment of miR-146a expression level were done using quantitative real-time PCR in all participants. MiR-146a rs2910164 GG genotype and the G allele were reported in 47% and 70% of the IBD patient group, respectively. And they were associated with increased IBD risk. All the IBD patients with the CC genotype (100%) and most of those with the CG genotype (66.67%) had an inactive disease, while most IBD patients with the GG genotype (73.68%) had an active disease. The miR-146a expression level was the highest with the CC genotype and the lowest with the GG genotype. Also, miR-146a expression level decreased significantly in IBD patients than controls and with disease activity. Combined detection of fecal calprotectin with miR-146a expression level improved the diagnostic sensitivity and the negative predictive value in differentiating IBD patients with active disease from those inactive.Our study identified a strong association of miR-146a rs2910164 GG genotype and G allele with IBD-increased susceptibility and activity in the Egyptian population. The miR-146a rs2910164 polymorphism can reduce miR-146a expression levels in these patients as well. Further research on a larger sample size and different ethnic populations can be the key to progress in establishing this genetic association.

Relationship between rs1410996 polymorphism of CFH gene and essential hypertension patients of Han from Yunnan Province.

To explore the relationship between rs1410996 polymorphism of CFH gene and essential hypertension (EH) in the Yunnan Han population. rs1410996 of CFH gene was genotyped based on the collected clinical phenotypes of the EH patients (n = 520) and healthy people (n = 494). On the genotype model and dominance model, there was no relationship between rs1410996 of CFH gene and EH after adjustment (P > 0.05). On the dominance model of male EH patients, the pulse pressure (PP) level of CC genotype carriers was higher than that of (CT + TT) genotype carriers after adjustment (P < 0.05). rs1410996 of CFH gene has no correlation with the genetic susceptibility to EH in the Yunnan Han population, but it is related to the PP level in male patients.

Полиморфизм гена GDF5 крупного рогатого скота калмыцкой породы и его влияние на экстерьерные показатели

Purpose. Study of the influence of polymorphism of GDF5 gene of Kalmyk cattle on exterior characteristics. Materials and Methods. The polymorphism of the GDF5 gene was examined in 60 individuals of Kalmyk cattle breed belonging to the APC “Plodovitoe” of the Maloderbetovsky district of the Republic of Kalmykia. DNA samples were isolated from whole blood collected from the jugular vein using an automated extraction method. Real-time polymerase chain reaction was performed to determine the T586C polymorphism of the GDF5 gene. Results. Among the studied herd of cattle, individuals with the TT genotype predominated - they accounted for 68.3% of the total. Animals with TC and CC genotypes accounted for 21.7 and 10.0%, respectively. The frequency of occurrence of the T allele of GDF5 gene was 0.792, which exceeded the frequency of the C allele (0.208) by 58.2%. The observed frequency of the TT and CC genotypes exceeded the expected ones by 5.6 and 5.7%, respectively. At the same time, the frequency of the TC genotype was lower than expected by 11.2%. Individuals with the TT genotype of the GDF5 gene were superior to their peers with the TC and CC genotypes in all measured parameters. Conclusion. TT genotype of GDF5 gene in the studied livestock of Kalmyk cattle breed, owned by the APC “Plodovitoye”, occurs with the highest frequency (0.683). A positive effect of the TT genotype of GDF5 gene on linear physique measurements of Kalmyk cattle was revealed.

Associations of the PPARα and Lipoprotein Lipase Enzyme Gene Polymorphisms with Dyslipidemia in Obese and Non-obese Males.

Peroxisome proliferator-activated receptor α (PPARα) is a nuclear transcription factor responsible for gene expression, particularly those associated with lipid metabolism. The lipoprotein lipase enzyme (LPL) is considered a key enzyme in lipid metabolism and transport. The link between dyslipidemia and obesity is well understood. Dyslipidemia is also an established risk feature for cardiovascular disease. Thus, it becomes progressively essential to identify the role of genetic factors as risk markers for the development of dyslipidemia among obese males. A case-control study was performed including 469 males. Anthropometric characteristics and serum lipid profiles such as triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were evaluated. Genomic DNA extraction and purification were performed using whole blood samples. Restriction enzyme fragment length polymorphism was used to genotype PPARα and LPL single nucleotide polymorphisms. The associations between these polymorphisms and dyslipidemia were examined. The CC and CG genotypes of PPARα gene polymorphisms were significantly associated with higher TC and LDL-C levels (P<0.05). The TT genotype of the LPL gene polymorphism was significantly associated with higher TG levels and lower HDL-C levels (P<0.05). In contrast, the GG genotype may have a protective action against dyslipidemia. The study reaches the interesting conclusion that there was a significant association between PPARα as well as LPL gene polymorphisms and dyslipidemia among obese and non-obese males.

The Association of Vitamin D Receptor Gene Polymorphism with Polycystic Ovary Syndrome in a Southeast Iranian Population

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women of reproductive age, characterized by hyperandrogenism, amenorrhea, and polycystic ovaries. Metabolic disorders, including insulin resistance (IR), are common comorbidities of PCOS, with vitamin D receptors playing a crucial role. Objectives: We investigated whether the rs2228570T &gt; C variant of the vitamin D receptor (VDR) gene is associated with the risk of PCOS. Methods: In the current study, 112 women with PCOS and 150 healthy women participated. Genomic DNA was extracted using the standard salting-out method. Genotyping of rs2228570T &gt; C was conducted via amplification-refractory mutation system polymerase chain reaction. Additionally, VD3 levels were measured using the ELISA system. Statistical analysis of genotyping data was performed using the SPSS V.22 package. Results: The statistical analysis showed that the T-allele of rs2228570C/T significantly decreased the risk of PCOS. Moreover, the T-allele in the codominant model significantly eliminated the risk of PCOS in our population. Our results also showed a statistically significant difference in VD3 levels between the CC and TT genotypes. Conclusions: Based on our result, rs228570C/T had a protective role for PCOS risk in our population.

Association of Genetic Profile with Muscle Mass Gain and Muscle Injury Prevention in Professional Football Players after Creatine Supplementation.

In recent years, the study of creatine supplementation in professional athletes has been of great interest. However, the genetics involved in response to supplementation is unknown. The aim of this study was to analyse, for the first time, the relationship between muscle performance-related genes and the risk of an increased body mass index (BMI) and muscle mass and a decrease in fat mass in professional football players after creatine supplementation. For this longitudinal study, one hundred and sixty-one men's professional football players were recruited. The polymorphisms ACE I/D, ACTN3 c.1729C>T, AMPD1 c.34C>T, CKM c.*800A>G, and MLCK (c.49C>T and c.37885C>A) were genotyped using Single-Nucleotide Primer Extension (SNPE). To assess the combined impact of these six polymorphisms, a total genotype score (TGS) was calculated. The creatine supplementation protocol consisted of 20 g/day of creatine monohydrate for 5 days (loading dose) and 3-5 g/day for 7 weeks (maintenance dose). Anthropometric characteristics (body mass index (BMI), fat, and muscle mass) were recorded before and after the creatine supplementation protocol. Characteristics of non-contact muscle injuries during the 2022/2023 season were classified according to a consensus statement for injury recording. The results showed that the allelic frequencies of ACE and AMPD1 differed between responders and non-responders in muscle mass increase (all p < 0.05). Players with a TGS exceeding 54.16 a.u. had an odds ratio (OR) of 2.985 (95%CI: 1.560-5.711; p = 0.001) for muscle mass increase. By contrast, those with a TGS below 54.16 a.u. had an OR of 9.385 (95%CI: 4.535-19.425; p < 0.001) for suffering non-contact muscle injuries during the season. The increase in BMI and muscle mass in response to creatine supplementation in professional football players was influenced by a TGS derived from the combination of favourable genotypes linked to muscle performance. The CC genotype and C allele of AMPD1 were particularly associated with a higher likelihood of muscle mass increase under creatine supplementation in this group of professional football players.

Genetic Polymorphisms of GP1BA, PEAR1, and PAI-1 may be Associated with Serum sIgE and Blood Eosinophil Levels in Chinese Patients with Allergic Diseases.

It has been suggested that genetic factors may be substantially linked to allergy disorders. This study aims to investigate the relationship between the serum specific Immunoglobulin E (sIgE), blood eosinophil, and the polymorphisms of glycoprotein Ib alpha gene (GP1BA) rs6065, platelet endothelial aggregation receptor 1 gene (PEAR1) rs12041331, and plasminogen activator inhibitor 1 gene (PAI-1) rs1799762. From the Peking Union Medical College Hospital, this study enrolled 60 healthy participants and 283 participants with allergic diseases. TaqMan-minor groove binder (MGB) quantitative polymerase chain reaction (qPCR) was used to examine the gene polymorphisms in each group. The TaqMan-MGB qPCR results were completely consistent with the DNA sequencing results, according to other studies in this medical center (Kappa =1, p <0.001). The GP1BA rs6065, PEAR1 rs12041331, and PAI-1 rs1799762 polymorphisms did not show different distribution between allergy patients and healthy individuals. Concerning allergy patients, the CT (n=33) genotype of GP1BA rs6065 had higher blood eosinophil level than the CC (n=250) genotype (0.59, IQR 0.32-0.72 vs 0.31, IQR 0.15-0.61, *109/L, p =0.005). The serum sIgE of AA (n=46) genotype of PEAR1 rs12041331 was lower (median 3.7, interquartile quartiles (IQR) 0.2-16.8, kU/L) than the GA (n=136) and GG (n=101) genotypes (GA median 16.3, IQR 3.1-46.3, kU/L, p = 0.002; GG median 12.9, IQR 3.0-46.9, kU/L, p =0.003). The GA genotypes of PEAR1 rs12041331were with higher blood eosinophil levels (median 0.42, IQR 0.17-0.74 *109/L) than the AA genotype (median 0.25, IQR 0.15-0.41*109/L, p =0.012). The sIgE of the 5G5G (n=44) genotype of PAI-1 rs1799762 was lower (median 5.0, IQR 0.1-22.8, kU/L) than the 4G5G (n=144) (median 17.3, IQR 3.7-46.0, kU/L, p = 0.012). The GP1BA rs6065, PEAR1 rs12041331, and PAI-1 rs1799762 polymorphisms may be associated with the genetic susceptibility of serum sIgE or blood eosinophil in Chinese allergic disease patients.

Potentially functional variants of ERRFI1 in hypoxia-related genes predict survival of non-small cell lung cancer patients.

Hypoxia is often involved in tumor microenvironment, and the hypoxia-induced signaling pathways play a key role in aggressive cancer phenotypes, including angiogenesis, immune evasion, and therapy resistance. However, it is unknown what role genetic variants in the hypoxia-related genes play in survival of patients with non-small cell lung cancer (NSCLC). We evaluated the associations between 16,092 single-nucleotide polymorphisms (SNPs) in 182 hypoxia-related genes and survival outcomes of NSCLC patients. Data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial were used as the discovery dataset, and the Harvard Lung Cancer Susceptibility (HLCS) Study served as the replication dataset. We also performed additional linkage disequilibrium analysis and a stepwise multivariable Cox proportional hazards regression analysis in the PLCO dataset. An independent SNP, ERRFI1 rs28624 A > C, was identified with an adjusted hazards ratio (HR) of 1.31 (95% CI = 1.14-1.51, p = 0.0001) for overall survival (OS). In further analyses, unfavorable genotypes AC and CC, compared with the AA genotype, were associated a worse OS (HR = 1.20, 95% CI = 1.03-1.39, p = 0.014) and disease-specific survival (HR = 1.21, 95% CI = 1.04-1.42, p = 0.016). Further expression quantitative trait loci analysis indicated that ERRFI1 rs28624C genotypes were significantly associated with higher ERRFI1 mRNA expression levels in the whole blood. Additional analysis showed that high ERRFI1 mRNA expression levels were associated with a worse OS in patients with lung adenocarcinoma. Our findings suggest that genetic variants in the hypoxia-related gene ERRFI1 may modulate NSCLC survival, potentially through their effect on the gene expression.

Macrophage-Stimulating 1 Polymorphism rs3197999 in Pediatric Patients with Inflammatory Bowel Disease.

Background and Objectives: Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), often necessitates long-term treatment and hospitalizations and also may require surgery. The macrophage-stimulating 1 (MST1) rs3197999 polymorphism is strongly associated with the risk of IBD but its exact clinical correlates remain under investigation. We aimed to characterize the relationships between the MST1 rs3197999 genotype and the clinical characteristics in children and adolescents with IBD within a multi-center cross-sectional study. Materials and Methods: Clinical data included serum C-reactive protein (CRP), albumin, activity indices (PUCAI, PCDAI), anthropometric data, pharmacotherapy details, surgery, and disease severity. Genotyping for rs3197999 was carried out using TaqMan hydrolysis probes. Results: The study included 367 pediatric patients, 197 with Crohn's disease (CD) (40.6% female; a median age of 15.2 years [interquartile range 13.2-17.0]) and 170 with ulcerative colitis (UC) (45.8% female; a median age of 15.1 years [11.6-16.8]). No significant relationships were found between MST1 genotypes and age upon first biologic use, time from diagnosis to biological therapy introduction, PUCAI, PCDAI, or hospitalizations for IBD flares. However, in IBD, the height Z-score at the worst flare was negatively associated with the CC genotype (p = 0.016; CC: -0.4 [-1.2-0.4], CT: -0.1 [-0.7-0.8], TT: 0.0 [-1.2-0.7)]). The TT genotype was associated with higher C-reactive protein upon diagnosis (p = 0.023; CC: 4.3 mg/dL [0.7-21.8], CT 5.3 mg/dL [1.3-17.9], TT 12.2 mg/dL [3.0-32.9]). Conclusions: This study identified links between MST1 rs3197999 and the clinical characteristics of pediatric IBD: height Z-score and CRP. Further studies of the associations between genetics and the course of IBD are still warranted, with a focus on more extensive phenotyping.

A mutation in POLR2A gene associated with body size traits in Dezhou donkeys revealed with GWAS.

The Dezhou donkey is a famous local donkey breed in China. The aim of the present study was to identify the genes associated with the body size traits of the Dezhou donkey and facilitate the breeding activities of the donkeys. A total of 349 donkeys from 2 generations (113 individuals in F0 and 236 in F1) were analyzed with restriction-site-associated DNA sequencing. A genome-wide association study revealed that the region between 13.7 and 15.6Mb of chromosome 13 is significantly associated with body sizes. Candidate genes related to body size development, including POLR2A, CHRNB1, FGF11, and ZBTB4, were identified. The results of GO and KEGG analysis indicated that the genes involved in many GO terms were related to metabolic processes and developmental processes. Additionally, a T>C mutation (Chr13:14312485) was found at intron 10 of the POLR2A gene. The association analysis showed significant differences among genotypes for the size traits. The body size of the individuals with the TT genotype was significantly higher than that with the CC genotype. The results showed that the polymorphism of POLR2A has the potential to be used as a marker in the breeding programs of the Dezhou donkeys.

The Association of Genetic Markers Involved in Muscle Performance Responding to Lactate Levels during Physical Exercise Therapy by Nordic Walking in Patients with Long COVID Syndrome: A Nonrandomized Controlled Pilot Study.

Several genetic markers have shown associations with muscle performance and physical abilities, but the response to exercise therapy is still unknown. The aim of this study was to test the response of patients with long COVID through an aerobic physical therapy strategy by the Nordic walking program and how several genetic polymorphisms involved in muscle performance influence physical capabilities. Using a nonrandomized controlled pilot study, 29 patients who previously suffered from COVID-19 (long COVID = 13, COVID-19 = 16) performed a Nordic walking exercise therapy program for 12 sessions. The influence of the ACE (rs4646994), ACTN3 (rs1815739), AMPD1 (rs17602729), CKM (rs8111989), and MLCK (rs2849757 and rs2700352) polymorphisms, genotyped by using single nucleotide primer extension (SNPE) in lactic acid concentration was established with a three-way ANOVA (group × genotype × sessions). For ACE polymorphism, the main effect was lactic acid (p = 0.019). In ACTN3 polymorphism, there were no main effects of lactic acid, group, or genotype. However, the posthoc analysis revealed that, in comparison with nonlong COVID, long COVID increased lactic acid concentrations in Nordic walking sessions in CT and TT genotypes (all p < 0.05). For AMPD1 polymorphism, there were main effects of lactic acid, group, or genotype and lactic acid × genotype or lactic acid × group × genotype interactions (all p < 0.05). The posthoc analysis revealed that, in comparison with nonlong COVID, long COVID increased lactic acid concentrations in Nordic walking sessions in CC and CT genotypes (all p < 0.05). Physical therapy strategy through Nordic walking enhanced physical capabilities during aerobic exercise in post-COVID19 patients with different genotypes in ACTN3 c.1729C>T and AMPD1 c.34C>T polymorphisms. These findings suggest that individuals who reported long COVID who presumably exercised less beforehand appeared to be less able to exercise, based on lactate levels, and the effect of aerobic physical exercise enhanced physical capabilities conditioned by several genetic markers in long COVID patients.

A descriptive study of the single-nucleotide polymorphisms known to affect the Tacrolimus trough concentration per dose, among a population of kidney failure patients in a tertiary hospital in Ghana

BackgroundThe burden of chronic kidney disease (CKD) and kidney failure in Ghana is on the ascendency, with the prevalence of CKD estimated at 13.3%. Patients with CKD who progress to kidney failure require life sustaining kidney replacement therapy (KRT) which is almost exclusively available in Ghana as haemodialysis. Kidney transplantation is considered the best KRT option for patients with irreversible kidney failure due to its relative cost efficiency as well as its superiority in terms of survival and quality of life. However, because transplants may trigger an immune response with potential organ rejection, immunosuppressants such as tacrolimus dosing are required.ObjectiveThis study sought to determine single nucleotide polymorphisms in CYP3A5, CYP3A4 and MDR1 genes that affect the pharmacokinetics of Tacrolimus in a population of Ghanaian patients with kidney failure.MethodThis cross-sectional study comprised of 82 kidney failure patients undergoing maintenance haemodialysis at the Renal and Dialysis unit of Korle-Bu Teaching Hospital (KBTH). Clinical and demographic data were collected and genomic DNA isolated. Samples were genotyped for specific SNPs using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP).ResultsParticipants, 58/82 (70.73%) harbored the wildtype CYP3A5*1/*1 AA genotype, 20/82 (24.39%) carried the heterozygous CYP3A5*1/*3 AG genotype, and 4/82 (4.88%) had the homozygous mutant CYP3A5*3/*3 GG genotype. Also, 6/82 (7.32%) carried the wildtype AA genotype, 11/82 (13.41%) had the heterozygous AG genotype, and 65/82 (79.27%) harbored the homozygous mutant GG genotype of CYP3A4*1B (-290 A>G). For MDR1_Ex21 (2677 G>T), 81/82 (98.78%) carried the wildtype GG genotype, while 1/82 (1.22%) had the heterozygous GT genotype. For MDR1_Ex26 (3435 C>T), 63/82 (76.83%) had the wildtype CC genotype, while 18/82 (21.95%) carried the heterozygous CT genotype, and 1/82 (1.22%) harbored the mutant TT genotype.ConclusionSNPs in CYP3A4, CYP3A5, and MDR1 genes in a population of Ghanaian kidney failure patients were described. The varying SNPs of the featured genes suggest the need to consider the genetic status of Ghanaians kidney failure patients prior to transplantation and tacrolimus therapy.

Exploring the Association of Biochemical Characterization and Genetic Determinants of TNF-α, CXCR2, and CCR5 Delta 32 Mutation with Predisposition to Polycystic Ovary Syndrome.

In this case control study, we used amplification-refractory mutation system (ARMS)-PCR to detect and determine the presence of the polymorphic variants TNF-α, CCR5-delta32, and CXCR2 in the study subjects. These gene polymorphs may serve as critical candidate gene variants in PCOS pathogenesis and therapeutics. The case-control study's findings revealed that the majority of the biochemical and endocrine serum biomarkers examined in the investigation-including lipids (LDL, HDL, and cholesterol), T2DM markers (fasting glucose, free insulin, and HOMA-IR), and hormones (FSH, LH, testosterone, and progesterone)-exhibited statistically significant changes in PCOS patients. The distributions of TNF-α (rs1800629), CCR5-delta32, and CXCR2 (rs2230054) genotypes analyzed within PCOS patients and healthy controls in the considered population were significant (p < 0.05). The heterozygosity of CXCR2-CA, TNF-α GA, and CCR5(WT+Δ32*) genotypes was significantly associated with PCOS susceptibility, with high OR and p < 0.05 in the codominant model. Similarly, the A allele of the TNF-α and CXCR2 genes, along with the CCR5Δ32*(mutant) allele, was significantly associated with PCOS susceptibility, with high OR and p < 0.05. Likewise, the CXCR2 (CA+AA) vs CC genotype was associated with increased susceptibility to PCOS, with OR 2.25, p < 0.032. Our study concludes that TNF-α rs1800629G>A, CXCR2-rs2230054C>T, and CCR5-Delta32 rs333 are potential loci for developing PCOS in the Tabuk population. These findings might eventually be useful in identifying and classifying those who are at risk for PCOS. To validate these results, it is advised that further longitudinal studies be conducted in diverse ethnic populations and with larger sample sizes.

Association of rs4588 polymorphism in vitamin D binding protein gene with polycystic ovarian syndrome in Iranian women: a case-control study

ObjectiveVitamin D deficiency and variations in the vitamin D binding protein (VDBP) gene may play a role in the development of Polycystic ovary syndrome (PCOS). This study aims to investigate the association of the rs4588 polymorphism with PCOS in Iranian women, as well as its association with infertility and recurrent pregnancy loss (RPL) in these patients.ResultsThe analysis revealed statistically significant differences in the distributions of genotypes and alleles of the rs4588 polymorphism among the three groups (p < 0.0001). The AC genotype and A allele showed an association with an elevated risk of PCOS and infertility. In this study, no association was found between genotypes and alleles of the rs4588 polymorphism and the risk of RPL in women with PCOS. Subjects with the AA or AC genotype exhibited significantly higher levels of LDL compared to those with the CC genotype.

Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) rs2071559 Gene Polymorphism and the Risk of Gliomas: A Systematic Review and Meta-Analysis.

A glioma is a form of tumor that is abundant in blood vessels. Vascular endothelial growth factor receptor (VEGFR) and its receptor 2 (VEGFR2) are important in the process of angiogenesis. The relationship between VEGFR2 rs2071559 and glioma development is currently uncertain. The present study aims to analyze the correlation between VEGFR2 rs2071559 gene polymorphism and the susceptibility to gliomas. A thorough search was carried out in the Cochrane Library, Scopus, and Medline databases from inception until 20 February 2024 using a mix of pertinent keywords. We used random-effects models to examine the odds ratio (OR) and reported the results together with their respective 95% confidence intervals (CIs). A total of six studies were incorporated. The results of our meta-analysis indicated that all genetic models of VEGFR2 rs2071559 gene polymorphism, starting from dominant (OR 1.40; p < 0.00001), recessive (OR 1.52; p < 0.0001), CC genotype (OR 1.78; p < 0.00001), CT genotype (OR 1.30; p < 0.0001), and C allele (OR 1.41; p < 0.00001), were associated with a higher risk of developing gliomas. The subgroup analysis revealed a higher OR for studies with a sample size of ≥500, originated from Asia, with a mean age of ≥42.3 years, and a male prevalence of <57%. This study suggests that VEGFR2 rs2071559 gene polymorphism is associated with a higher risk of gliomas.

Genetic variants of LncRNAs HOTTIP and MEG3 influence nasopharyngeal carcinoma susceptibility and clinicopathologic characteristics in the Southern Chinese population

ObjectiveRecent studies have indicated that HOTTIP and MEG3 are associated with the initiation and progression of various types of tumors, including nasopharyngeal carcinoma (NPC). This investigation aimed to elucidate the impact of HOTTIP and MEG3 polymorphisms on the susceptibility and clinicopathologic characteristics of NPC.MethodsThis research employed next-generation sequencing and multiplex PCR to assess the polymorphisms of HOTTIP rs1859168 and MEG3 rs7158663 in 200 NPC and 200 healthy individuals respectively. HOTTIP and MEG3 expression were assessed via qRT-PCR assessment. Furthermore, the genotypes and alleles frequency of rs1859168 and rs7158663 were compared between healthy and NPC individuals to elucidate their influence on NPC susceptibility and relation with clinicopathologic characteristics.ResultsIn comparison with the healthy cohort, the presence of HOTTIP rs1859168 CC genotype and the C allele were markedly linked with increased NPC incidence (p < 0.05). Furthermore, the MEG3 rs7158663 AA genotype and the A allele also indicated an increased risk of NPC (p < 0.05). The subgroup analysis of age, EBV infection, gender, nationality, smoking, and drinking status revealed no marked association between rs1859168 and rs7158663 genotypes and these potential confounding factors. Moreover, it was observed that rs1859168 CC and rs7158663 AA genotypes were related to local tumor invasion and lymph node metastasis. Additionally, HOTTIP indicated a marked elevation, while MEG3 substantially reduced in NPC samples than the normal nasopharyngeal biospecimens. Patients who carried CC or CA genotypes rather than the HOTTIP rs1859168 AA genotype, had substantially higher HOTTIP levels, while patients with rs7158663 AA or GA genotypes indicated notably lower expression of MEG3 than GG genotype carriers.ConclusionIndividuals with genetic variants of HOTTIP rs1859168 and MEG3 rs7158663 might have an increased risk of NPC susceptibility and related clinicopathologic characteristics, potentially by affecting the expression of HOTTIP and MEG3.

The association between endoplasmic reticulum aminopeptidase 2 gene single nucleotide polymorphisms and the risk of psoriasis and psoriatic arthritis in Egyptians.

Psoriasis (Ps) is a disorder attributed to the immune system that involves inflammation of the skin and joints. Psoriasis is a multifactorial disorder in which genetic factors represent about 70% of the disease risk. This study aims to establish the correlation between the ERAP2 gene's single nucleotide polymorphisms (SNPs) rs2910686 and rs2248374 with the susceptibility to Ps and/or psoriatic arthritis (PsA) among the Egyptian population. Genotyping of ERAP2 gene SNPs (rs2910686 and rs2248374) in 120 psoriatic patients with and without arthritis and 100 controls was done using real-time PCR. The genotype frequency and distribution of the ERAP2 SNP (rs2910686 and rs2248374) were in Hardy-Weinberg equilibrium (HWE). For rs2910686, the TC and CC genotypes and C allele frequency were significant risk factors for PsA compared to the controls (OR = 5.708, OR = 10.165, and OR = 4.282, respectively). They also were significant risk factors for Ps compared to the controls (OR = 5.165, OR = 5.040, and OR = 3.258, respectively). For rs2248374, the AG genotype significantly increased the risk of PsA (OR = 2.605) and Ps (OR = 3.768) compared to controls. The AG genotype was significantly related to the risk of Ps (OR = 3.369) G allele with PsA (OR = 1.608) and Ps (OR = 1.965) compared to controls. In Egyptian individuals, the ERAP2 gene polymorphisms (rs2248374 and rs2910686) may contribute genetically to the pathophysiology of psoriasis and PsA.

Exploring the relationship between caffeine metabolism-related CYP1A2 rs762551 polymorphism and team sport athlete status and training adaptations

BackgroundThis study aimed to achieve a dual objective: to compare the frequencies of CYP1A2 rs762551 genotypes between team sport athletes and a control group, and to determine the association between the rs762551 polymorphism and changes in physical performance after a six-week training program among elite basketball players.MethodsThe study encompassed an analysis of 504 individuals, comprising 320 athletes and 184 controls. For the Turkish cohort, DNA was isolated using the buccal swab method, and genotyping was conducted using the KASP technique. Performance assessments included the Yo-Yo IR2 and 30 m sprint tests. For Russian participants, DNA samples were extracted from peripheral blood, a commercial kit was used for DNA extraction, and genotyping of the rs762551 polymorphism was conducted using DNA microarray.ResultNotably, a statistically significant linear decline in the prevalence of the CC genotype was observed with ascending levels of athletic achievement within team sports (sub-elite: 18.0%, elite: 8.2%, highly elite: 0%; p = 0.001). Additionally, the CA genotype was the most prevalent genotype in the highly elite group compared to controls (80.0% vs. 45.1%, p = 0.048). Furthermore, statistically significant improvements in Yo-Yo IR2 performance were noted exclusively among basketball players harboring the CA genotype (p = 0.048).ConclusionsThe study’s findings indicate that the rs762551 CC genotype is a disadvantage in elite team sports, whereas the CA genotype provides an advantage in basketball performance.

Association between a single-nucleotide polymorphism of the angiotensin-converting enzyme gene and susceptibility to systemic lupus erythematosus in the Hainanese population of China.

The angiotensin-converting enzyme (ACE) gene plays a significant role in regulating immune responses and inflammatory processes, thus impacting the susceptibility to systemic lupus erythematosus (SLE). Understanding how single-nucleotide polymorphisms (SNPs) within the ACE gene contribute to the genetic susceptibility to SLE is essential for comprehending the disease's aetiology. Therefore, exploring this relationship in the Hainan region of China is crucial for gaining insights into the pathogenesis of SLE. This study comprised 428 participants, including 214 SLE patients and 214 healthy controls. Clinical data were gathered, and blood samples were collected. Genotyping of three SNPs (rs4459609, rs4309, rs1987692) within the ACE gene was performed using SNaPshot technology. The frequencies of alleles and genotypes of these three SNPs were compared between the SLE and control groups. Combining different genetic models and haplotype analysis, the correlation between ACE gene polymorphisms and SLE was investigated. Both study groups exhibited conformity with the Hardy-Weinberg genetic equilibrium (p>.05). Significant differences were observed in the genotype frequency distributions of ACE genes rs4459609, rs4309 and rs1987692 between the SLE and control groups (p=.009,.008,.032, respectively). The frequency of allele T at rs4309 was significantly higher in the SLE group than in the control group, correlating significantly with increased SLE risk (odds ratio [OR]=1.527, 95% confidence interval [CI]=1.147-2.035). Associations among ACE rs4459609, rs4309 and rs1987692 polymorphisms and increased susceptibility to SLE were found under co-dominant and dominant models (p<.05, with OR values and 95% CI greater than 1). Linkage disequilibrium was observed among rs4459609, rs4309 and rs1987692, and haplotype analysis revealed a significantly higher frequency of the CCA haplotype in the control group compared to the SLE group (p<.001). The ACA and ATA haplotypes showed significantly higher frequencies in the SLE group than in the control group (p=.014, p=.013, respectively). ACE gene polymorphisms are associated with the genetic susceptibility to SLE. The AC and AA genotypes at the rs4459609 locus, the TT genotype and T allele at the rs4309 locus and the AC and CC genotypes at the rs1987692 locus may serve as risk factors for the development of SLE.

THE SIGNIFICANCE OF GENE POLYMORPHISM OF SOME PRO- AND ANTIINFLAMMATORY CYTOKINES IN PATIENTS WITH SEVERE ULCERATIVE COLITIS

The objective of the study was too study the polymorphism of TNFa(rs1800629), IL10(1800871, 1800896) ITGA4(rs1143674, rs1449263), ITGB7(rs11574532) genes in patients with severe ulcerative colitis (UC) Materials and methods. The study included 70 people with UC who lived in the Irkutsk region, the Republic of Buryatia and the Zabaikalsky krai. Patients were divided into two groups: patients receiving genetically engineered biological therapy (GIBT; n = 22) and patients receiving basic therapy (n=48). The control consisted of 115 healthy volunteers. The genotypes were studied by real-time PCR. For statistical processing, we used the criterion χ2, the odds ratio (OR), binary logistic regression analysis with the calculation of 95% confidence interval (CI) using the program "IBM SPSS Statistics Version 25.0". Results. Homozygotes of ITGA4(rs1449263)GG had 2.5 times higher chances of developing the disease than carriers of other polymorphic variants (OR = 2,580; 95% CI: 1,129-5,898; χ2 = 5,266; p = 0,022). Patients with extracellular manifestations (ECM) were 3 times more likely to receive GIBT (OR = 3,000; 95% CI: 0,982-9,167; χ2 = 3,878; p = 0,049). IL10 media(1800896)AA prevailed in the group of patients receiving basic therapy (OR = 0,282; 95% CI: 0,089-0,890; χ2 = 5,473; p = 0,020). Subjects with the homozygous variant of ITGA4(rs1143674)CC were 3.5 times more likely to have indications for the administration of GIBT (OR = 3,536; 95% CI: 1,077-11,603; χ2 = 4,576; p = 0,033). The results of binary logistic regression demonstrated that the homozygous genotype of ITGA4(rs1143674)CC and extraintestinal manifestations of the disease were predictors for an unfavorable prognosis of UC accompanied by the GIBT administration. Conclusion. The association of the debut of the disease, smoking, polymorphic variants TNFa(rs1800629), IL10(1800871), ITGB7(rs11574532) with the UC development and clinical manifestations was not revealed. The disease developed 2,5 times faster in homozygote ITGA4(rs1449263)GG than in other genotype carriers. Subjects with polymorphic variant IL10(1800896)AA prevailed in the group of patients with basic therapy. In addition to the previously known extraintestinal manifestations of the disease, the ITGA4 genotype (rs1143674) CC can act as a risk factor for the development of severe UC, requiring the GIBT administration.