Association Of Single Nucleotide Polymorphisms Research Articles

Genetic variants in folate metabolism-related genes, serum folate and hepatocellular carcinoma survival: the Guangdong Liver Cancer Cohort study.

Folate metabolism is involved in the development and progression of various cancers. We investigated the association of single nucleotide polymorphisms (SNP) in folate-metabolising genes and their interactions with serum folate concentrations with overall survival (OS) and liver cancer-specific survival (LCSS) of newly diagnosed hepatocellular carcinoma (HCC) patients. We detected the genotypes of six SNPin three genes related to folate metabolism: methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR). Cox proportional hazard models were used to calculate multivariable-adjusted hazard ratios (HR) and 95 % CI. This analysis included 970 HCC patients with genotypes of six SNP, and 864 of them had serum folate measurements. During a median follow-up of 722 d, 393 deaths occurred, with 360 attributed to HCC. In the fully-adjusted models, the MTRR rs1801394 polymorphism was significantly associated with OS in additive (per G allele: HR = 0·84, 95 % CI: 0·71, 0·99), co-dominant (AG v. AA: HR = 0·77; 95 % CI: 0·62, 0·96) and dominant (AG + GG v. AA: HR = 0·78; 95 % CI: 0·63, 0·96) models. Carrying increasing numbers of protective alleles was linked to better LCSS (HR10–12 v. 2–6 = 0·70; 95 % CI: 0·49, 1·00) and OS (HR10–12 v. 2–6 = 0·67; 95 % CI: 0·47, 0·95). Furthermore, we observed significant interactions on both multiplicative and additive scales between serum folate levels and MTRR rs1801394 polymorphism. Carrying the variant G allele of the MTRR rs1801394 is associated with better HCC prognosis and may enhance the favourable association between higher serum folate levels and improved survival among HCC patients.

Association of ACE2 Gene Variants with Adverse Perinatal Outcomes in COVID-19 Infected Pregnant Women in Kazakhstan

SARS-CoV-2 utilizes the angiotensin-converting enzyme 2 (ACE2) receptors located on membranes to enter host cells. Nevertheless, the ACE2 gene primarily encodes for a zinc metalloproteinase, which is a part of the renin–angiotensin system (RAS). ACE2 downregulation results in the deregulation of RAS in favor of pro-fibrosis, pro-apoptosis, oxidative stress, pro-inflammation, aldosterone production and release, and blood vessel contraction axis. ACE2 is highly expressed in the placenta. There are both axes of the RAS system in the placenta. This study aims to assess the perinatal outcomes with ACE2 receptor polymorphisms in pregnant women infected with SARS-CoV-2 during pregnancy. The case-control study was conducted to determine the association of ACE2 single-nucleotide polymorphisms in 171 COVID-19-positive pregnant subjects and 112 control subjects. The recessive mutations of rs2158082 and rs4830974 were associated with an increased risk of low birthweight and preterm birth, whereas the dominant mutation of rs2285666 (CT + TT) was associated with decreased odds of low birthweight. COVID-19 was not a significant factor contributing to the adverse perinatal outcomes in our sampling. These findings may help to clarify the controversy regarding the increased risk of adverse perinatal outcomes observed during COVID-19 as well as provide new perspectives for research on the genetic factors associated with a higher risk of adverse perinatal outcomes.

Combining single nucleotide polymorphisms and gene expression of LEP, FABP4, STAT5A and DGAT1 genes for improvement of body weight in Holstein calves

The objective of this study was to investigate the possible association of single nucleotide polymorphisms and gene expression of leptin (LEP), fatty acid binding protein (FABP4), signal transducer and activator of transcription 5A (STAT5A) and diacylglycerol acyltransferase (DGAT1) genes with body weight in Holstein calves. For the RNA extraction process, blood samples from 100 Holstein bull calves were taken. According to farm records, the acquired bull calves were weaned at a body weight of roughly 90 kg, with birth weights ranging from 31 to 38 kg and weaning ages ranging from 60 to 100 days. To account for the non-genetic causes, the dairy calves' body weight was changed to their 205-day body weight. Nucleotide sequence changes in the form of SNPs were found in the LEP, FABP4, STAT5A, and DGAT1 genes in the investigated Holstein calves. The identified SNPs and corrected 205-day body weight showed a significant correlation (P < 0.05). According to ΔCT values, a significant relationship between the mRNA levels of the LEP, FABP4, STAT5A, and DGAT1 genes and body weight was also found (P < 0.05). The effectiveness of the LEP, FABP4, STAT5A, and DGAT1 genes as proxies for growth qualities in Holstein dairy calves is highlighted by this study. Therefore, it was possible to select an animal with a high rate of growth.

Strong association of single nucleotide polymorphisms in BRCA1, ATM, and CHEK2 with breast cancer susceptibility in a sub-population of Iranian women.

Breast cancer (BC) is the most prevalent malignancy in females worldwide. Mutations in the DNA repair pathway genes contribute to a significant increase in BC risk. The present study aimed to assess the frequency of polymorphisms in BRCA1, ATM, and CHEK2 genes and their association with BC susceptibility in the Kurdish population from the West of Iran. In the present case-control study, the distribution of single nucleotide polymorphisms (SNPs) in CHEK2 (rs17879961), ATM (rs28904921), and BRCA1 (rs80357906, rs1555576855, rs1555576858, and rs397509247) genes were investigated in 335 BC cases and 354 healthy-matched controls by Taqman allelic discrimination assay. The chi-square goodness-of-fit test was employed for the assessment of Hardy-Weinberg Equation. Relative risk and odds ratios were calculated based on the Koopman asymptotic score and the Baptista-Pike method, respectively. Also, the sensitivity and specificity of each polymorphism were assessed using the Wilson-Brown test and a P-value < 0.05 indicating significant differences between the two groups in all assessments. Data showed there was a strong association between rs397509247 (OR = 7.53, 95% CI 1.88-90.91, p = 0.004), rs1555576858 (OR = 10.53, 95% CI 0.01-0.51, p = 0.0005), and rs80357906 (OR = 6.33, 95% CI 0.05-0.043, p < 0.0001) in BRCA1 gene and rs17879961 (OR = 3.52, 95% CI 0.084-0.946, p = 0.02) in CHEK2 gene, with BC risk in the population of interest. Among these, rs28904921 in ATM gene demonstrated the strongest association (OR = 72.66, 95% CI 0.007-0.214, p < 0.0001). This suggests that these SNPs, particularly rs28904921, are significantly associated with an increased risk of BC in the studied population. Our results indicated that BRCA1, ATM, and CHEK2 polymorphisms have a high frequency in the Iranian breast cancer population, with some mutant allele frequencies being much higher than those reported in other populations. We have also provided a simple, multiplex, rapid, and accurate genotyping assay that is useful in clinical settings.

Association of WNT Gene Polymorphism with Frequency of Cytogenetic Disorders under the Action of Ionizing Radiation

The paper presents the results of a study of the association of single nucleotide polymorphisms of the WNT genes with an increased frequency of cytogenetic disorders in the blood lymphocytes of workers at an ionizing radiation facility exposed to long-term radiation exposure at doses of 100–500 mGy.The object of the study was the blood of 95 apparently healthy workers who were subjected to long-term technogenic external exposure to γ-radiation in doses from 100 to 500 mGy in the course of their professional activities. For all examined individuals, a standard cytogenetic analysis of blood lymphocytes was performed. Genomic DNA was isolated from workers’ blood lymphocytes using a “QIAamp DNA Blood mini Kit” (Qiagen, Germany). DNA was genotyped for 116 single nucleotide polymorphisms of the WNT genes using high-density “CytoScan™ HD Array” (Affymetrix, USA) chips (DNA chips). Taking into account the Bonferroni correction, an association of single nucleotide polymorphisms of the WNT genes with a high frequency of circular chromosomes in blood lymphocytes was established, all other types of cytogenetic disorders did not show statistical significance. As a result of the study, a single nucleotide polymorphism of the WNT9B gene rs1530364 was identified, which can be considered as a potential marker of individual radiosensitivity.

Ischemic stroke susceptibility associated with ALPK1 single nucleotide polymorphisms by inhibiting URAT1 in uric acid hemostasis

ObjectivesIschemic stroke (IS) prevalence rising annually, the necessity of discovering non-interventional genetic influences is progressing. Single nucleotide polymorphism (SNP) plays a pivotal role in stable inheritance of disease susceptibility. Based on the relationship between Alpha- Kinase 1 (ALPK1) and traditional IS risk factors especially hyperuricemia, our study investigated the association and function of ALPK1 SNPs with IS susceptibility. MethodsA case-control study of 1539 patients and 933 controls from northeast China was conducted. Genotyping information of ALPK1 rs2074379 and rs2074388 was collected. Four types of plasmids including rs2074379/rs2074388 G/G, A/G, G/A, and A/A were transfected into 293T cells to observe ALPK1 and SLC22A12 expression. Possible ALPK1 structures of different SNPs were predicted online. ResultsGenotype GG (OR = 1.371, CI = 1.029–1.828, P = 0.031) and GA (OR = 1.326, CI = 1.110–1.584, P = 0.002) of rs2074379 and GA of rs2074388 (OR = 1.359, CI = 1.137–1.624, P = 0.001) were found significantly susceptible to IS, with G allele on sites to be a risk allele. Rs2074379 had a multiplicative interaction with hyperuricemia (OR = 1.637, CI = 1.157–2.315, P = 0.005). Uric acid levels differed in genotypes (P < 0.001). The expression of ALPK1 (P < 0.01) and SLC22A12 in membrane urate transporter 1 (URAT1) protein (P < 0.05) functionally changed with G allele on either site. With glycine changing into aspartic acid at rs2074388, the protein secondary structure changed, but the ALPK1 protein subtype remained still. ConclusionsALPK1 rs2074379 and rs2074388 SNPs were functionally associated with IS susceptibility. The wild allele progressed IS risk probably by reducing ALPK1 expression and inhibiting URAT1 raising the uric acid level, contributing to further exploration of pathogenetic mechanisms of stroke.Chinese Clinical Trial Registration number: ChiCTR-COC-17013559.

Impact of Chondroitin Sulfate Proteoglycan 4 Pseudogene 12 Genetic Variants on Colorectal Cancer Risk: A Case-Control Study.

This study aims to investigate the correlation between the chondroitin sulfate proteoglycan 4 pseudogene 12 (CSPG4P12) polymorphism and the risk of colorectal cancer (CRC). This case-control study involved 850 patients with CRC and 850 health controls. The genotypes of CSPG4P12 (rs2880765, rs6496932, and rs8040855) were determined by the TaqMan-MGB probe method. Logistic regression model was employed to evaluate the association of CSPG4P12 single-nucleotide polymorphisms (SNPs) with the risk of CRC by calculating the odds ratio (OR) and 95% confidence interval (CI). The CSPG4P12 exhibited lower expression in CRC tissues. Our data showed that the rs6496932 variant increased CRC risk (CA vs. CC: p = 0.006; CA + AA vs. CC: p = 0.005). In contrast, the rs8040855 variant reduced the risk of CRC (CG vs. CC: p < 0.001; CG + GG vs. CC: p < 0.001). Stratification by gender and age revealed that the rs8040855 variant decreased CRC risk; however, the rs6496932 variant increased CRC risk among males (CA vs. CC: p = 0.024; CA + AA vs. CC: p = 0.014) and younger individuals (CA vs. CC: p = 0.004; CA + AA vs. CC: p = 0.010). When stratified by smoking and drinking status, the rs8040855 variant decreased CRC risk among nonsmokers (CG vs. CC: p < 0.001; CG + GG vs. CC: p < 0.001) and nondrinkers (CA vs. CC: p = 0.002; CA + AA vs. CC: p = 0.004). The rs6496932 variant increased CRC risk among nonsmokers (CA vs. CC: p = 0.016; CA + AA vs. CC: p = 0.036) and nondrinkers (CG vs. CC: p < 0.001; CG + GG vs. CC: p < 0.001). Haplotype analysis showed that the CSPG4P12 Trs2880765Crs6496932Grs8040855 haplotype reduced the risk of CRC compared with the reference haplotype (CSPG4P12 Ars2880765Crs6496932Crs8040855) (OR = 0.46, 95% CI = 0.26-0.82, p = 0.049). These findings highlight the potential of these genetic variants as biomarkers for CRC susceptibility, offering insights into personalized prevention strategies.

Association of ADIPOQ Single Nucleotide Polymorphisms (SNPs) with Obesity Risk in Different Populations: A Systematic Review and Analysis

Background: Thirty-two single nucleotide polymorphisms (SNPs) are commonly found in ADIPOQ. APN levels are decreased in obesity, and SNPs of the ADIPOQ gene affecting APN have varying associations with the development of obesity in different populations. This systematic review and meta-analysis aimed to investigate the association of SNPs in ADIPOQ with the risk of obesity development in various populations. Methods: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist date up to Feb 2023. We used the Newcastle–Ottawa scale to find out if a study fit the main criteria for submission and to assess the data quality of the articles included in the systematic review and meta-analysis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated via Review Manager (RM) V.5.4 to estimate the connection between ADIPOQ polymorphic qualities of a gene and the risk of developing obesity. Results: The present study analysed the association between ADIPOQ polymorphisms (rs1501299, rs2241766, rs266729, rs822393, and rs822396) and obesity risk and suggested that APN is partially responsible for the emergence of obesity and increases its risk. Conclusion: It is important to take into account several limitations of this meta-analysis when evaluating the findings. First off, even though we looked through numerous databases for all relevant papers, there is a chance we overlooked some. Our capacity to arrive at more firm conclusions was further hampered by the small number of papers that made up our meta-analysis. The most current data, however, are presented in this study since it used newly published data to perform a meta-analysis and evaluate the relationship between ADIPOQ polymorphisms and obesity.

Association of polymorphisms in the HTRA1 gene with myopia

PurposeTo evaluate the associations of single-nucleotide polymorphisms (SNPs) in the high-temperature requirement protease A 1 (HTRA1) gene with myopia.Methods25 SNPs in HTRA1 were selected, including 23 haplotype-tagging SNPs, SNP rs2142308...

ApaI Polymorphism in the Vitamin D Receptor Gene Decreases the Risk of Perianal Fistulas in Crohn’s Disease

Background: Vitamin D, through the activation of its receptor (VDR), plays an immunomodulatory role in the gastrointestinal tract. Single-nucleotide polymorphisms (SNPs) in the VDR gene have been associated with Crohn’s disease (CD) risk, and patients carrying the TaqI polymorphism in this gene run a higher risk of developing a penetrating behavior. Aims: We analyzed the association of BsmI, ApaI, TaqI, and FokI SNPs in the VDR gene with the clinical characteristics of CD. Methods: Four polymorphisms identified in the VDR gene (BsmI, FokI, ApaI, and TaqI) were genotyped in blood samples from CD patients (n = 115) by using PCR-RFLP. The disease’s location and behavior and the presence of perianal fistulas were collected from each patient. Intestinal fibroblasts from ileal resections of CD patients (n = 10) were genotyped, and the expression of fibrotic and inflammatory markers was analyzed by RT-PCR. Results: The data reveal no association between any of the polymorphisms and CD risk. A strong linkage disequilibrium was detected between TaqI and both ApaI and BsmI, which in turn were strongly associated. Homozygosis or heterozygosis for the a allele of the ApaI SNP or b allele of the BsmI SNP was significantly associated with a lower risk of a penetrating behavior, while the aa genotype was associated with a lower risk of perianal fistulas. Fibroblasts carrying the aa genotype expressed lower levels of fibrotic and inflammatory markers. Conclusion: The aa genotype of the ApaI SNP in the VDR gene is associated with a lower risk of perianal fistulas in CD and a reduced expression of fibrotic and inflammatory markers in intestinal fibroblasts.

Association of vitamin D receptor gene polymorphisms with caries risk in children: a systematic review and meta-analysis

BackgroundTo investigate the association of vitamin D receptor (VDR) gene polymorphism with caries risk in children(< 18 years).MethodsThe electronic databases PubMed, Cochrane, EMBASE, Web of Science, CNKI, Cqvip, and Wanfang were searched for observational studies on the relationship between VDR single nucleotide polymorphism(SNP) and caries, including cohort, case–control, and cross-sectional studies. Quality assessment of selected studies was conducted using the Newcastle Ottawa scale. Odds ratios (OR) with 95% confidence intervals (CI) values for associations of individual VDR SNP with dental caries were calculated based on four genetic models: allelic, recessive, dominant, and over-dominant.ResultsOf 79 studies considered, 10 (nine case–control and one cross-sectional) were selected for analysis; the studies involved seven VDR SNPs: ApaI(rs7975232),BsmI(rs1544410),FokI(rs2228570),TaqI(rs731236), TaqI/BglI(rs739837), FokI(rs10735810) and Cdx-2(rs11568820). Alleles C and T of FokI(rs10735810) were significantly differently distributed in the caries and caries-free groups (OR = 1.33, 95% CI: 1.30–2.30, P = 0.03), with CC + CT genotypes at this locus associated with greater risk of developing caries than the TT genotype (OR = 1.87, 95%CI: 1.15–3.04, P = 0.01). Further, TT + CC genotype at TaqI(rs731236) was associated with a 1.33-fold higher risk of caries development than the TC genotype (OR = 1.33, 95%CI: 1.06–1.67, P = 0.02). On subgroup analysis, the association between TaqI(rs731236) and caries risk was affected by dentition type, and ethnicity (permanent dentition: OR = 1.48, 95%CI: 1.07–2.03, P = 0.02; Asian: OR = 1.38, 95%CI: 1.02–1.87, P = 0.03;). Genotype distributions at BsmI(rs1544410), TaqI/BglI(rs739837), FokI(rs2228570), and ApaI(rs7975232) did not differ significantly between the caries and caries-free groups.ConclusionsCaries risk could be associated with TaqI(rs731236) and FokI(rs10735810) genotypes, and TaqI(rs731236) may be a risk factor for permanent teeth caries among Asian people.

Effects and interaction of single nucleotide polymorphisms at the pharmacokinetic/pharmacodynamic site: insights from the Rotterdam study into metformin clinical response and dose titration.

Our study investigated the impact of genetic variations on metformin glycemic response in a cohort from the Rotterdam Study, comprising 14,926 individuals followed for up to 27 years. Among 1285 metformin users of European ancestry, using linear mixed models, we analyzed the association of single nucleotide polymorphisms (SNPs) and a Polygenic Risk Score (PRS) with glycemic response, measured by changes in metformin dosage or HbA1c levels. While individual genetic variants showed no significant association, rs622342 on SLC2A1 correlated with increased glycemic response only in metformin monotherapy patients (β = -2.09, P-value < 0.001). The collective effect of variants, as represented by PRS, weakly correlated with changes in metformin dosage (β = 0.023, P-value = 0.027). Synergistic interaction was observed between rs7124355 and rs8192675. Our findings suggest that while higher PRS correlates with increased metformin dosage, its modest effect size limits clinical utility, emphasizing the need for future research in diverse populations to refine genetic risk models.

Association between the Val66Met (rs6265) polymorphism of the brain-derived neurotrophic factor (BDNF) gene, BDNF protein level in the blood and the risk of developing early‑onset Parkinson's disease.

Brain-derived neurotrophic factor (BDNF) is involved in the maintenance of dopamine level and the survival of dopaminergic neurons, which may affect the functionality of brain structures responsible for motor and cognitive function. The aim of the study was to assess the association of individual and combined single nucleotide polymorphism (SNP) in the rs6265 BDNF (Val66Met), rs397595 DAT (SLC6A3), and rs4680 COMT (Val158Met) genes with early‑onset of Parkinson's disease (PD) patients. Moreover, we assessed the association between the BDNF Val66Met polymorphism and the level of BDNF protein in the serum of patients with PD and controls. The study involved 163 patients with idiopathic PD divided into early onset (<55 years) and late‑onset (>55 years) groups and 91 healthy age‑matched people (Control). The SNP were determined using the TaqMan Real‑Time PCR method. Serum BDNF levels were determined by ELISA assay. The risk of developing early PD in people with the BDNF genotype AG increases threefold in comparison with the carriers of the BDNF genotype GG. In PD patients and healthy people with the BDNF genotypes AG and AA, a lower serum BDNF level was found compared to those with the BDNF genotype GG in both groups. The results of our study indicate that the presence of the Val66Met BDNF gene polymorphism is associated with reduced blood BDNF levels and an elevated risk of developing early‑onset PD. This effect appears to be more pronounced in men.

The serotonin 1A receptor promoter polymorphism, rs6295, is associated with morphofunctional features

Introduction. The tendency to weight gain is influenced by many genetic and environmental factors (nutrition, level of physical activity, social well-being, etc.), as well as complex interactions of these factors. Studying the genetic factors of obesity can help in developing individual strategies for the prevention and treatment of this common disease. One of the most important hereditary factors is the neurotransmitter systems gene polymorphism, (including the serotonin system gene polymorphism). The aim of the investigation is to study the associations of single nucleotide polymorphism of the rs6295 locus of the serotonin receptor gene 1A HTR1A with morphofunctional features and body weight gain. Material and methods. The study used the materials of a comprehensive anthropogenetic examination of 386 men and 418 women aged 17 to 30 years. More than 20 morphofunctional indicators were measured using the traditional anthropometric method. The material for genetic analysis was genomic DNA isolated from buccal epithelium. The reliability of intergroup differences was assessed using the Mann-Whitney criterion, while canonical discriminant analysis was used to study intergroup variability. Results. For the first time, a significant correlation was shown between the polymorphism of the serotonin receptor type 1 gene HTR1A and morphofunctional features: individuals with the G/G genotype with greater body weight have lower (compared to carriers of the C/C and C/G genotypes) values of the indicators of the level of metabolic processes and specific metabolism. Conclusion. The statistically significant obtained results may be used in the development of individual strategies for the prevention and treatment of obesity, and also allow us to supplement the information on the association of serotonin system gene polymorphism with morphofunctional features and contribute to expanding our understanding of the human physique features formation and their relationships with hereditary predisposition.

Association of Walking Pace and Risk of Stroke: A Two- Sample Mendelian Randomization Study in a European Ancestry Cohort.

Walking pace (WP), a simple physiological indicator, has been found to be strongly associated with a variety of health outcomes in recent years. Among them, the relationship between walking pace and stroke is of particular interest. Given the high morbidity, disability and mortality associated with stroke, identifying modifiable indicators of health, such as walking pace, could help in stroke prevention strategies. However, the causal relationship between WP and stroke risk remains unclear. This study aims to determine the causal relationship between walking pace and risk of stroke using a two-sample Mendelian randomization approach in a European-ancestry population. In order to evaluate the potential for a causal relationship between WP and stroke in people of European heritage, a two-sample Mendelian randomization (MR) study was carried out. Statistics about the association of single nucleotide polymorphisms (SNPs) with stroke were taken from FinnGen (R8) (n = 284,040), while the UK Biobank genome-wide association studies (GWAS) provided the summary data on the association of SNPs with WP (n = 459,915). The inverse-variance weighted (IVW) method was utilised as the primary strategy to examine the causal connection between WP and stroke. Additionally, complementary analyses were conducted using the MR-Egger and weighted median. In order to identify the potential directional pleiotropy and heterogeneity, the MR-Egger intercept test, the MR-PRESSO test, and Cochran's Q statistic were all carried out. This connection was evaluated using OR with 95% confidence intervals (CIs). A total of 48 SNPs were identified as valid instrumental variables in our two-sample MR analysis. The result showed that a slower walking pace is associated with a higher risk of stroke (OR = 0.573; 95% CI, 0.383-0.858, P = 0.007). The "leave-one-out" analysis demonstrated that the absence of a single SNP did not affect the robustness of our results. The MR-Egger intercept test indicated that genetic pleiotropy did not introduce bias into the results [intercept = -2.9E-03, SE = 0.008, P = 0.719] and Cochran's Q test revealed no heterogeneity. Therefore, the sensitivity analyses yielded comparable results. Consequently, the results of the sensitivity analyses were consistent. Our MR study revealed that WP is inversely associated with risk of stroke. These results provided evidence that slower WP causally increased the risk of stroke, recommending that patients with lower WP should have a prompt physical examination and targeted interventions to reduce their risk of stroke and enhance their quality of life.

Association of superoxide dismutase and catalase genetic variants and their gene-gene interactions with the severity of COVID-19

BACKGROUND: Since the outbreak of COVID-19 infection, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), oxidative stress has been proposed as an important player in its severity. This increased the interest in studying antioxidant systems to evaluate their possible role in counteracting disease progression. AIM: The aim of the current study was to investigate the association of single nucleotide polymorphism (SNP) of superoxide dismutase (SOD) and catalase (CAT) genes with the severity of COVID-19. MATERIALS AND METHODS: Study subjects were divided into two groups based on the severity of their symptoms. Allele-specific PCR was used for genotyping, and multifactor dimensionality reduction (MDR) analysis was performed to investigate the SNP–SNP interaction models. RESULTS: The results showed a significant association of SOD2 rs4880 with the severity of COVID-19 (p = 0.002). SOD2 47TT genotype was significantly more frequent among patients with severe COVID-19 (OR 4.34; 95% CI 1.72–10.96). The three-locus SNP–SNP interaction model, resulted from MDR analysis, was statistically significant (0.55 × 10–4, OR 3.81; 95% CI 1.96–7.42). Carriers of SOD1 7958G * SOD2 47T * CAT 262C allele combination had a higher risk of severe COVID-19 (p = 0.0045, OR 2.84, 95% CI 1.40–5.78). CONCLUSIONS: The obtained results contribute to better understanding of COVID-19 pathogenesis and suggest novel potential prognostic biomarkers of the infection.

Transcriptomic Insights into the Atrial Fibrillation Susceptibility Locus near the MYOZ1 and SYNPO2L Genes

Genome-wide association studies have identified a locus on chromosome 10q22, where many co-inherited single nucleotide polymorphisms (SNPs) are associated with atrial fibrillation (AF). This study seeks to identify the impact of this locus on gene expression at the transcript isoform level in human left atria and to gain insight into potential causal variants. Bulk RNA sequencing was analyzed to identify myozenin 1 (MYOZ1) and synaptopodin 2-like (SYNPO2L) transcript isoforms and the association of common SNPs in this region with transcript isoform expression levels. Chromatin marks were used to suggest candidate regulatory SNPs in this region. Protein amino acid changes were examined for predicted functional consequences. Transfection of MYOZ1 and two SYNPO2L isoforms were performed to localize their encoded proteins in cardiomyocytes derived from stem cells. We identified one MYOZ1 transcript isoform and four SYNPO2L transcript isoforms, two of which encode proteins, while the other two encode long noncoding RNAs (lncRNAs). The risk allele of the strongest AF susceptibility SNP on chromosome 10q22 is associated with decreased MYOZ1 expression and increased expression of the two SNYPO2L lncRNA isoforms. There are many SNPs co-inherited with the top AF-associated SNP due to linkage disequilibrium (LD), including rs11000728, which we propose as the MYOZ1 regulatory SNP, confirmed by reporter gene transfection. In addition, this LD block includes three missense SNPs in the SYNPO2L gene, with the minor protective haplotype predicted to be detrimental to protein function. MYOZ1 and both protein isoforms of SYNPO2L were localized to the sarcomere. This is a complex locus with the potential for several SNPs in a haplotype to alter AF susceptibility by opposing effects on MYOZ1 and SYNPO2L lncRNA expression, along with effects on SYNPO2L protein function.

Genetic associations with neural reward responsivity to food cues in children.

To test associations of candidate obesity-related single nucleotide polymorphisms (SNPs) and obesity polygenic risk scores (PRS) with neural reward reactivity to food cues. After consuming a pre-load meal, 9-12-year-old children completed a functional magnetic resonance imaging (fMRI) paradigm with exposure to food and non-food commercials. Genetic exposures included FTO rs9939609, MC4R rs571312, and a pediatric-specific obesity PRS. A targeted region-of-interest (ROI) analysis for 7 bilateral reward regions and a whole-brain analysis were conducted. Independent associations between each genetic factor and reward responsivity to food cues in each ROI were evaluated using linear models. Analyses included 151 children (M = 10.9 years). Each FTO rs9939609 obesity risk allele was related to a higher food-cue-related response in the right lateral hypothalamus after controlling for covariates including the current BMI Z-score (p < 0.01), however, the association did not remain significant after applying the multiple testing correction. MC4R rs571312 and the PRS were not related to heightened food-cue-related reward responsivity in any examined regions. The whole-brain analysis did not identify additional regions of food-cue-related response related to the examined genetic factors. Children genetically at risk for obesity, as indicated by the FTO genotype, may be predisposed to higher food-cue-related reward responsivity in the lateral hypothalamus in the sated state, which, in turn, could contribute to overconsumption. https://clinicaltrials.gov/study/NCT03766191, identifier NCT03766191.

FCGR2/3 polymorphisms are associated with susceptibility to Kawasaki disease but do not predict intravenous immunoglobulin resistance and coronary artery aneurysms.

Kawasaki disease (KD) is a pediatric vasculitis that can result in coronary artery aneurysm (CAA) formation, which is a dangerous complication. Treatment with intravenous immunoglobulin (IVIg) significantly decreases the risk of CAA, possibly through competitive binding to Fc-gamma receptors (FcγRs), which reduces the binding of pathological immune complexes. However, ~20% of children have recrudescence of fever and have an increased risk of CAA. Therefore, we aimed to identify genetic markers at the FCGR2/3 locus associated with susceptibility to KD, IVIg resistance, or CAA. We investigated the association of single-nucleotide polymorphisms (SNPs) and copy number variations (CNVs) at the FCGR2/3 locus with KD susceptibility, IVIg resistance, and CAA risk using a family-based test (KD susceptibility) and case-control analyses (IVIg resistance and CAA risk) in different cohorts, adding up to a total of 1,167 KD cases. We performed a meta-analysis on IVIg resistance and CAA risk including all cohorts supplemented by previous studies identified through a systematic search. FCGR2A-p.166His was confirmed to be strongly associated with KD susceptibility (Z = 3.17, p = 0.0015). In case-control analyses, all of the investigated genetic variations at the FCGR2/3 locus were generally not associated with IVIg resistance or with CAA risk, apart from a possible association in a Polish cohort for the FCGR3B-NA2 haplotype (OR = 2.15, 95% CI = 1.15-4.01, p = 0.02). Meta-analyses of all available cohorts revealed no significant associations of the FCGR2/3 locus with IVIg resistance or CAA risk. FCGR2/3 polymorphisms are associated with susceptibility to KD but not with IVIg resistance and CAA formation. Currently known genetic variations at the FCGR2/3 locus are not useful in prediction models for IVIg resistance or CAA risk.

Investigation of the relationship between adiponectin gene polymorphism (ADIPOQ SNP rs-266729) and obesity Patients / Basra-Iraqi

Adiponectin is one of the most important hormones secreted by adipose tissue and plays a major role in the development of obesity. A variant-specific ADIPOQ single nucleotide polymorphism (SNP rs-266729) with a C to G missense mutation can be strongly associated with obesity. Therefore, this study aims to evaluate the association of single nucleotide polymorphisms (SNP rs-266729) of the ADIPOQ gene with obesity and some biochemical markers in these patients. The case-control study included 186 participants (106 patients and 80 healthy control). DNA was extracted from whole blood and then the Restriction Fragment Length Polymorphism Polymerase Chain Reaction (RFLP-PCR) technique was used to limit the genotype of the ADIPOQ gene (rs266729) polymorphism. Also, the lipid profile, glycated hemoglobin (HbA1C), fasting blood glucose (FBG), insulin, and adiponectin were measured by standard methods. Results: The allele G in the ADIPOQ-gene polymorphism (rs266729) was a significantly higher frequency of 23 (21.6%) in the obese patients (P_Value = 0.039) compared with the control subject of 10 (12.5%). It significantly increased the risk in the additive model and allele frequency (P = 0.0139 and 0.0133), respectively. The rs266729 SNP showed a significant association with increased BMI, insulin, HOMO-IR, TG, VLDL, and lower adiponectin at a p-value of 0.001 for all, after adjustments for age and sex. Lower levels of high-density lipoprotein (HDL) were observed in the CG and GG genotypes compared to the ADIPOQ rs266729 SNP C.C genotype (p = 0.032). In obese individuals, there was no significant relationship between rs266729 SNP and HbA1C, FBS, TC, and LDL. In conclusion, the single nucleotide polymorphism (rs266729) of the ADIPOQ gene has a significant difference with BMI, insulin, TG, VLDL, and HOMO-IR in obese patients, which might be the cause of obesity.