Allele Comparison Research Articles

Comparison of MCM6 rs4988235 Polymorphism Allele and Genotype Frequencies in Professional Football Players and a Sedentary Control Group

Comparison of MCM6 rs4988235 Polymorphism Allele and Genotype Frequencies in Professional Football Players and a Sedentary Control Group

The association between XPD rs13181 and rs1799793 polymorphism and oral cancer risk: evidence from a meta-analysis

ObjectiveSingle nucleotide polymorphisms (SNPs) are common in genes and can lead to dysregulation of gene expression in tissues, which can affect carcinogenesis. Many studies reporting the association between xeroderma pigmentosum group D (XPD) polymorphisms of rs13181 and rs1799793 with oral cancer risk, but with conflicting and inconclusive results.MethodsWe performed a comprehensive and systematic search through the PubMed, Elsevier, Web of science, and Embase databases, twelve studies were included in the meta-analysis to determine whether XPD rs13181 and rs1799793 polymorphism contributed to the risk of oral cancer.ResultsThe pooled date indicated a significant association between the rs13181 polymorphism and oral cancer risk for the allele comparison model (odds ratio, OR = 1.60, 95% confidence intervals, CI = 1.09–2.35, P = 0.02), the dominant model (OR = 1.74, 95% CI = 1.08–2.82, P = 0.02), and the heterozygote model (OR = 1.59, 95% CI = 1.02–2.49, P = 0.04). For the XPD rs1799793 polymorphism, it is not associated with the incidence of oral cancer under any model. Subgroup analyses based on ethnicity indicated that the rs13181 polymorphism increased the risk of oral cancer among Asians according to the allele comparison model (OR = 1.97, 95% CI = 1.10–3.51, P = 0.02), the dominant model (OR = 2.35, 95% CI = 1.25–4.44, P = 0.008), the heterozygote model (OR = 2.05, 95% CI = 1.15–3.66, P = 0.01), and the homozygous model (OR = 2.47, 95% CI = 1.06–5.76, P = 0.04).ConclusionOur meta-analysis suggests a positive correlation between XPD rs13181polymorphism and the development of oral cancer among Asians, but a negative correlation among Caucasians populations.

Exploring the origin of a unique mutant allele in twin-tail goldfish using CRISPR/Cas9 mutants

Artificial selection has been widely applied to genetically fix rare phenotypic features in ornamental domesticated animals. For many of these animals, the mutated loci and alleles underlying rare phenotypes are known. However, few studies have explored whether these rare genetic mutations might have been fixed due to competition among related mutated alleles or if the fixation occurred due to contingent stochastic events. Here, we performed genetic crossing with twin-tail ornamental goldfish and CRISPR/Cas9-mutated goldfish to investigate why only a single mutated allele—chdS with a E127X stop codon (also called chdAE127X)—gives rise to the twin-tail phenotype in the modern domesticated goldfish population. Two closely related chdS mutants were generated with CRISPR/Cas9 and compared with the E127X allele in F2 and F3 generations. Both of the CRISPR/Cas9-generated alleles were equivalent to the E127X allele in terms of penetrance/expressivity of the twin-tail phenotype and viability of carriers. These findings indicate that multiple truncating mutations could have produced viable twin-tail goldfish. Therefore, the absence of polymorphic alleles for the twin-tail phenotype in modern goldfish likely stems from stochastic elimination or a lack of competing alleles in the common ancestor. Our study is the first experimental comparison of a singular domestication-derived allele with CRISPR/Cas9-generated alleles to understand how genetic fixation of a unique genotype and phenotype may have occurred. Thus, our work may provide a conceptual framework for future investigations of rare evolutionary events in domesticated animals.

The FGFR2 Variant rs13387042 is Associated With Breast Cancer Risk: A Meta-Analysis and Systematic Review

ObjectiveThe association of FGFR2-rs13387042 polymorphism with breast cancer (BC) susceptibility in women remains inconclusive due to varying reports. In this study, we conducted a meta-analysis to explore the relationship between FGFR2-rs13387042 polymorphism and susceptibility to BC. MethodsRelevant literature were acquired through searches across multiple databases. Odds ratio (OR) values were pooled to assess the risk of BC for different alleles and genotypes. The heterogeneity among the included literature was evaluated. Sensitivity analysis was used to verify the stability of the results. Egger's linear regression test was used to assess the significance of publication bias of the included literature. ResultsA total of 17 publications were included, encompassing 122,607 cases and 175,966 controls. There was significantly increased risk of BC for allele A compared with G (OR = 1.15, 95% CI = 1.14-1.67, P < .001), genotype AA compared with GG (OR = 1.34, 95% CI = 1.29-1.38, P < .001), and genotype GA compared with GG (OR = 1.19, 95% CI = 1.12-1.26, P < .001). Both Egger's test and funnel plot indicated the presence of publication bias. After adjusting potential publication bias by the trim-and-fill method, the comparison of allele A versus G (OR = 1.15, 95% CI = 1.13-1.17, P < .001), genotype AA versus GG (OR = 1.32, 95% CI = 1.28-1.37, P < .001), and genotype GA versus GG (OR = 1.15, 95% CI = 1.09-1.22, P < .001) remained statistically significant. In various subgroups, the allele A showed significantly higher risk of BC upon allele G in estrogen receptor (ER) positive BC, ER negative BC, progesterone receptor (PR) positive BC, PR negative BC, triple-negative BC, pathological grade I BC, grade II BC, and grade III breast cancer. The subsequent sensitivity analysis suggested the above findings stable and reliable. ConclusionIn this study, we found that the allele A of the FGFR2-rs13387042 polymorphism is associated with increased risk of developing breast cancer. This study underscores its potential as a genetic marker for personalized risk assessment and targeted interventions.

Whole genome sequencing of mouse lines divergently selected for fatness (FLI) and leanness (FHI) revealed several genetic variants as candidates for novel obesity genes

BackgroundAnalysing genomes of animal model organisms is widely used for understanding the genetic basis of complex traits and diseases, such as obesity, for which only a few mouse models exist, however, without their lean counterparts.ObjectiveTo analyse genetic differences in the unique mouse models of polygenic obesity (Fat line) and leanness (Lean line) originating from the same base population and established by divergent selection over more than 60 generations.MethodsGenetic variability was analysed using WGS. Variants were identified with GATK and annotated with Ensembl VEP. g.Profiler, WebGestalt, and KEGG were used for GO and pathway enrichment analysis. miRNA seed regions were obtained with miRPathDB 2.0, LncRRIsearch was used to predict targets of identified lncRNAs, and genes influencing adipose tissue amount were searched using the IMPC database.ResultsWGS analysis revealed 6.3 million SNPs, 1.3 million were new. Thousands of potentially impactful SNPs were identified, including within 24 genes related to adipose tissue amount. SNP density was highest in pseudogenes and regulatory RNAs. The Lean line carries SNP rs248726381 in the seed region of mmu-miR-3086-3p, which may affect fatty acid metabolism. KEGG analysis showed deleterious missense variants in immune response and diabetes genes, with food perception pathways being most enriched. Gene prioritisation considering SNP GERP scores, variant consequences, and allele comparison with other mouse lines identified seven novel obesity candidate genes: 4930441H08Rik, Aff3, Fam237b, Gm36633, Pced1a, Tecrl, and Zfp536.ConclusionWGS revealed many genetic differences between the lines that accumulated over the selection period, including variants with potential negative impacts on gene function. Given the increasing availability of mouse strains and genetic polymorphism catalogues, the study is a valuable resource for researchers to study obesity.

The association between polymorphism of LDL-R gene and ischemic stroke risk in Chinese population: A meta-analysis

ObjectiveLow-density lipoprotein receptor (LDL-R) gene polymorphisms have been indicated to be correlated with ischemic cerebrovascular disease including ischemic stroke susceptibility. However, the results from each published study are inconsistent. MethodsAll eligible case-control studies that met the search terms were retrieved in PubMed, Embase, Wanfang Med Online and Chinese National Knowledge Infrastructure (CNKI) databases. We identified seven independent case-control studies with a total of 10,355 subjects from Chinese population up to May 2023. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the susceptibility of ischemic stroke. ResultsMeta-analysis results indicated that rs1122608 polymorphism of LDL-R gene significantly decreased ischemic stroke risk under dominant model (OR = 0.69, 95% CI = 0.54–0.87), heterozygote comparison (OR = 0.69, 95% CI = 0.53–0.92) and allele comparison (OR = 0.74, 95% CI = 0.65–0.84) in overall analysis. Furthermore, pooled analysis showed that significant associations were observed between rs688 polymorphism and ischemic stroke risk in heterozygote carriers (OR = 1.71, 95% CI = 1.07–2.71) and dominant model (OR = 1.67, 95% CI = 1.04–2.68) in Chinese population. ConclusionsOur comprehensive meta-analysis on the role of LDL-R gene rs1122608 and rs688 polymorphisms in the risk of ischemic stroke revealed that the rs1122608 polymorphism was associated with a decreased risk, while the rs688 polymorphism was associated with an increased risk of ischemic stroke in Chinese population. Further multicenter studies were needed to confirm the effect on the susceptibility of ischemic stroke.

Association of MTHFR gene polymorphisms with non-Hodgkin lymphoma risk: Evidence from 31 articles.

Background: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms, particularly C677T and A1298C, have been implicated in various cancers, including non-Hodgkin lymphoma (NHL); however, their association with NHL risk remains inconclusive. Methods: We conducted an updated meta-analysis to assess the relationship between MTHFR gene polymorphisms (C677T and A1298C) and NHL risk. Relevant studies were identified through systematic literature searches in multiple databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations. Results: The meta-analysis included 32 studies (8222 cases vs. 12956 controls) for MTHFR C677T and 26 studies (6930 cases vs. 11611 controls) for the A1298C polymorphism. Our meta-analysis revealed no significant associations between MTHFR gene polymorphisms (C677T and A1298C) and NHL risk. However, subgroup analysis stratified by ethnicity and NHL subtype yielded interesting findings for the C677T polymorphism. Specifically, in the subgroup analysis of Caucasians, the C677T polymorphism was significantly associated with NHL risk (heterozygous: OR=1.16, 95% CI=1.02-1.32; allele comparison: OR=1.07, 95% CI=1.01-1.13). Furthermore, in the analysis stratified by NHL subtype, the C677T polymorphism was significantly associated with increased follicular lymphoma (FL) risk (homozygous: OR=1.25, 95% CI=1.02-1.53; recessive: OR=1.28, 95% CI=1.06-1.56). False-positive result possibility (FPRP) analysis verified that the association of the MTHFR C677T polymorphism with NHL risk for Caucasians and FL subtypes was a true positive and deserves attention. We also determined that the C677T polymorphism is an expression quantitative trait locus (eQTL) since it is associated with MTHFR gene expression. Conclusion: There was no overall association between MTHFR gene polymorphisms (C677T and A1298C) and NHL risk, but stratified analyses revealed significant associations in specific subgroups. While meta-analyses inherently build upon existing studies, our work distinguishes itself by incorporating recent data, applying rigorous analytical techniques, and providing more evidence of the MTHFR C677T polymorphism as an eQTL.

Update on the association of miR-149 rs2292832 C>T polymorphism with gastric cancer risk: A meta-analysis study of gastrointestinal cancers.

Single nucleotide polymorphisms in microRNAs are believed to affect the occurrence and progression of cancer by altering the expression and biological functions of microRNAs. Several studies investigated the role of the miR-149 rs2292832 C>T polymorphism on the risk of gastric cancer (GC), but got conflicting results. We performed a comprehensive and systematic search through the PubMed MEDLINE, Google Scholar, Science Direct, Scopus, CNKI, and Web of science, 8 studies were included in the meta-analysis to determine whether miR-149 rs2292832 C>T polymorphism contributed to the risk of GC. Pooled data indicated that miR-149 rs2292832 C>T polymorphism was not associated with GC risk. In the stratified analysis by ethnicity, miR-149 rs2292832 C>T polymorphism significantly increased GC risk under the allele comparison model (odds ratio [OR] = 1.27, 95% CI = 1.04-1.55, Pheterogeneity = 0.18, P = .02), recessive model (OR = 1.44, 95% CI = 1.04-2.01, Pheterogeneity = 0.19, P = .03) among Caucasians; but decreased GC risk under the allele comparison model (OR = 0.89, 95% CI = 0.81-0.98, Pheterogeneity = 0.22, P = .02) and dominant model (OR = 0.82, 95% CI = 0.72-0.93, Pheterogeneity = 0.15, P = .01) among Asian. Our meta-analysis suggests a positive correlation between miR-149 rs2292832 C>T polymorphism and GC development among Caucasians, but negative correlation among Asian population.

Association study of WNK1 genetic variants and essential hypertension risk in the Northern Han Chinese in Beijing.

Background: Essential hypertension (EH) is a complex disorder resulting from interaction of genetic and environmental factors. Lysine deficient protein kinase 1 (WNK1) plays a very important role in maintaining renal potassium, sodium and chlorine ions balance as well as the regulation of blood pressure, so the WNK1 gene is considered a key gene for EH. This study thus sought to evaluate possible genetic associations between the WNK1 genetic variants and EH risk in the Northern Han Chinese population in Beijing. Methods: This study included 476 hypertensive subjects and 491 normotensive subjects. A total of 12 tag SNVs of WNK1 gene were genotyped successfully by TaqMan assay. Comparisons of the genotypic and allelic frequency between cases and controls were made by using the chi-square test. Logistic regression analyses were performed under different genetic models, and haplotype analysis was also conducted. Results: A total of 12 SNVs were identified as the tag SNVs for WNK1 gene. Significant associations were observed between WNK1 gene rs7305099 variant and EH risk, and T allele influenced hypertension risk in a protective manner. After correcting for multiple testing using Bonferroni, the significance remained for the SNV of rs7305099 in three genetic models [allele comparison, p < 0.0002, OR = 0.627, 95%CI (0.491-0.801); homozygote comparison, p < 0.0003, OR = 0.278, 95%CI (0.140-0.552); additive model, p < 0.0003, OR = 0.279, 95%CI (0.140-0.553)]. In the haplotype analyses, we found that the haplotype A-A-A-C-G-G-G was significantly associated with increased risk for EH (p = 0.043, OR = 1.23). Conclusion: Our data suggested that the rs7305099 genetic variant and the haplotype A-A-A-C-G-G-G on WNK1 gene might be associated with the susceptibility of EH in the Northern Han Chinese population. These could provide evidences to the risk assessment, early prevention and individualized therapy of EH to some extent.

Update on the relationship between the SLC4A7 variant rs4973768 and breast cancer risk: a systematic review and meta-analysis.

This meta-analysis aimed to update knowledge about the association between the SLC4A7 variant rs4973768 and breast cancer incidence. Studies were identified from relevant digital databases. Fixed- or random-effects models were used to calculate odds ratios and 95% confidence intervals. Statistical Q and I2 tests and sensitivity analyses were used to detect interstudy heterogeneity and test the statistical stability of overall estimates, respectively. Egger's tests were applied to detect publication bias among included studies. In silico analysis was used to ascertain increased expression of SLC4A7 mRNA in rs4973768 with the mutant allele. Trial sequential analysis was used to calculate the study's sample size. The overall odds ratios reflected a positive correlation between the SLC4A7 rs4973768 polymorphism and susceptibility to breast cancer in five genetic comparisons of alleles T and C, and tests revealed significant heterogeneity in the allele comparison. After stratification by ethnicity, heterogeneity in Asian and White populations substantially decreased (Ph = 0.984, I2 = 0%) and remained stable (Ph = 0.083, I2 = 46.3%), respectively. The mutant allele was associated with increased expression of SLC4A7 mRNA in rs4973768. The cumulative z curve indicated that our conclusions were robust. Our updated consequence shows that the SLC4A7 rs4973768 polymorphism is associated with increased breast cancer risk.

Pharmacogenomic profile of actionable molecular variants related to drugs commonly used in anesthesia: WES analysis reveals new mutations.

Background: Genetic interindividual variability is associated with adverse drug reactions (ADRs) and affects the response to common drugs used in anesthesia. Despite their importance, these variants remain largely underexplored in Latin-American countries. This study describes rare and common variants found in genes related to metabolism of analgesic and anaesthetic drug in the Colombian population. Methods: We conducted a study that included 625 Colombian healthy individuals. We generated a subset of 14 genes implicated in metabolic pathways of common medications used in anesthesia and assessed them by whole-exome sequencing (WES). Variants were filtered using two pipelines: A) novel or rare (minor allele frequency-MAF <1%) variants including missense, loss-of-function (LoF, e.g., frameshift, nonsense), and splice site variants with potential deleterious effect and B) clinically validated variants described in the PharmGKB (categories 1, 2 and 3) and/or ClinVar databases. For rare and novel missense variants, we applied an optimized prediction framework (OPF) to assess the functional impact of pharmacogenetic variants. Allelic, genotypic frequencies and Hardy-Weinberg equilibrium were calculated. We compare our allelic frequencies with these from populations described in the gnomAD database. Results: Our study identified 148 molecular variants potentially related to variability in the therapeutic response to 14 drugs commonly used in anesthesiology. 83.1% of them correspond to rare and novel missense variants classified as pathogenic according to the pharmacogenetic optimized prediction framework, 5.4% were loss-of-function (LoF), 2.7% led to potential splicing alterations and 8.8% were assigned as actionable or informative pharmacogenetic variants. Novel variants were confirmed by Sanger sequencing. Allelic frequency comparison showed that the Colombian population has a unique pharmacogenomic profile for anesthesia drugs with some allele frequencies different from other populations. Conclusion: Our results demonstrated high allelic heterogeneity among the analyzed sampled, enriched by rare (91.2%) variants in pharmacogenes related to common drugs used in anesthesia. The clinical implications of these results highlight the importance of implementation of next-generation sequencing data into pharmacogenomic approaches and personalized medicine.

Interleukin-10 -1082 G/A polymorphism and its association with early or severe presentation of coronary artery disease: A systematic review and meta-analysis.

Interleukin-10 (IL-10) is an anti-inflammatory cytokine with potent deactivating properties on macrophages and T cells; and plays an important role in atherosclerotic plaque maturation and rupture. A guanine (G) to adenine (A) substitution in the IL-10 gene at -1082bp (rs1800896) has been associated with reduced in IL-10 production in vitro. Against this background, we tested the association of IL-10 -1082G/A with early or severe presentation of coronary artery disease (CAD) using a systematic review and updated meta-analysis of published association studies. Relevant studies were identified following a comprehensive online search on PubMed, EMBASE, MEDLINE, Scopus, Cochrane library and Web of Science databases and stratified into two subgroups based on mode of CAD presentation: early or severe and non-severe. Study level odds ratios (ORs) and their 95% confidence intervals (CI) were pooled using random effects employing a Z test. A total of 24 studies were included for quantitative synthesis with a cumulative sample of 19,135 (11,143 cases / 7,992 controls). A significant association was derived for IL-10 -1082G/A and early or severe CAD via dominant, recessive, and allelic genetic model comparisons [OR 1.24 (95% CI 1.02, 1.50), p=0.03; OR 1.32 (95% CI 1.03, 1.69), p=0.03 and OR 1.18 (95% CI 1.02, 1.36), p=0.02 respectively]. In contrast, no significant association was seen for the pooled group or non-severe CAD subgroup (p=NS). Sensitivity analysis showed consistent results. IL-10 -1082G/A appears to be associated with early or severe presentation of CAD. Further studies are warranted to confirm this association.

Investigation of Vitamin D Receptor Gene rs731236 Polymorphism in Turkish Rugby Players

Vitamin D is an important molecule responsible for the development, contraction and regeneration of muscles, and activates its biological functions by means of its receptors, the vitamin D receptor (VDR), which is a member of the nuclear receptor group. In the present study, we aimed to analyze the rs731236 distribution in Turkish rugby players. A total of 22 male players and 30 sedentary individuals (as a control group) participated in the study. Following DNA isolation, rs731236 polymorphisms of VDR was determined by real-time polymerase chain reaction (RT- PCR). Statistical analysis was carried out by chi-square test. CC, CT and TT genotype and percentage distributions for rs731236 polymorphism in players were as 5 (23%), 10 (45%) and 7 (32%), respectively. Allelic distributions were found to be 20 (45%) for C allele, and 24 (55%) for T allele. For the control group; CC, CT and TT genotypes and percentages were as 4 (13%), 17 (57%) and 9 (30%), respectively. C allele was counted as 25 (42%) and 35 (58%) for controls. When we compare athletes and control groups in the terms of genotypes, we detected no statistically significant difference (p= 0.12). For the allele comparison, we detected no significant difference between groups (p= 0.76). Determination of gene combinations in athletes is of great importance for carrying out of the optimal training programs. Therefore, we aimed to determine the distribution of the alleles related with athletic performance on successful athletes. In our cohort, the CT genotype and T allele were more intensely determined in players.

TNF-α promoter variant (G-308A) is associated with susceptibility to P. falciparum infection and severe malaria: a meta-analysis and trial sequential analysis

Tumor necrosis factor-alpha (TNF-α) plays an essential role in Plasmodium falciparum infection, with lower levels associated with susceptibility to infection and higher levels linked with organ failure in severe malaria. Genetic polymorphisms in the promoter region of the TNF-α gene (G-308A and G-238A) affect plasma TNF-α levels. Numerous case-control studies have been conducted to determine the possible association between TNF-α polymorphisms and susceptibility to malaria infection and clinical severity; however, the results are inconsistent. Various databases such as Google Scholar, Science Direct, PubMed, and Scopus were searched for relevant articles for the present meta-analysis. Data were extracted from the eligible studies based on inclusion and exclusion criteria. Meta-analysis was carried out with CMA v.3.3.070 software, and combined odds ratio, 95% confidence interval, and p values were calculated. Further, a trial sequential analysis was also performed to test whether enough number of case and controls have been enrolled to date to draw a valid conclusion. Allele (OR = 9.757, p value=.049) and heterozygous (OR = 8.98, p value=.016) comparison model revealed the TNF-α G-308A variant as a susceptible genetic factor for P. falciparum infection. Similarly, a significant association of TNF-α G-308A polymorphism with P. falciparum malarial severity was also observed (A versus G: OR = 1.761, p value = .000; and GG + GA versus GG: OR = 1.769, p value = .000). However, no association of TNF-α (G-238A) polymorphism was observed with infection and severity of P. falciparum or Plasmodium vivax malaria. TNF-α G-308A variant is associated with susceptibility to P. falciparum infection and clinical severity. However, further studies on different populations are required.

The association of cytokine gene polymorphisms with tuberculosis susceptibility in several regional populations.

By collecting the data of all relevant articles, the goal of this study was to better understand the relationship between the IL-6/IL-18 polymorphism and susceptibility to tuberculosis in several regional populations. Pubmed, Embase, WOS and CNKI were used to find relevant literature. The findings of separate research were merged using Review Manager. A total of 25 studies were included in this study. IL-6 rs1800795 (dominant. comparison: p-value<0.0001, OR 1.43, 95 % CI 1.23-1.67; recessive comparison: p-value<0.0001, OR 0.48, 95 % CI 0.35-0.65; allele comparison: p-value<0.0001, OR 1.43, 95 % CI 1.27-1.62), IL-18 rs1946518 (dominant comparison: p-value=0.01, OR 1.19, 95 % CI 1.04-1.35; recessive comparison: p-value=0.01, OR 0.82, 95 % CI 0.71-0.96; allele comparison: p-value=0.002, OR 1.14, 95 % CI 1.05-1.24), IL-18 rs187238 (dominant comparison: p-value=0.0002, OR 1.35, 95 % CI 1.15-1.58; allele comparison: p-value<0.0001, OR 1.31, 95 % CI 1.14-1.50). All gene polymorphisms were shown to be substantially linked to tuberculosis in the general population. Positive findings of rs187238 and rs1800795 polymorphisms were primarily driven by several regional populations, according to subgroup analyses. This meta-analysis found that the the IL-6 rs1800795and IL-18 rs187238 polymorphisms may have a role in TB susceptibility.

Alzheimer's Disease Risk Variant rs3865444 in the CD33 Gene: A Possible Role in Susceptibility to Multiple Sclerosis.

Polymorphisms in genes encoding receptors that modulate the activity of microglia and macrophages are attractive candidates for participation in genetic susceptibility to multiple sclerosis (MS). The aims of the study were to (1) investigate the association between Alzheimer’s disease-linked variant rs3865444:C>A in the CD33 gene and MS risk, (2) assess the effect of the strongest MS risk allele HLA-DRB1*15:01 on this association, and (3) analyze the correlation of rs3865444 with selected clinical phenotypes, i.e., age of onset and disease severity. CD33 rs3865444 was genotyped in a cohort of 579 patients and 1145 controls and its association with MS risk and clinical phenotypes was analyzed by logistic and linear regression analysis, respectively. Statistical evaluation revealed that rs3865444 reduces the risk of MS in the HLA-DRB1*15:01-positive subpopulation but not in the cohort negative for HLA-DRB1*15:01. A significant antagonistic epistasis between rs3865444 A and HLA-DRB1*15:01 alleles in the context of MS risk was detected by the interaction synergy factor analysis. Comparison of allele and genotype distribution between relapsing-remitting MS, secondary progressive MS, and control groups revealed that rs3865444 C to A substitution may also be associated with a decreased risk of transition of MS to its secondary progressive form, irrespective of the HLA-DRB1*15:01 carrier status. On the other hand, no correlation could be found between rs3865444 and the age of disease onset or MS severity score. Future studies are required to shed more light on the role of CD33 in MS pathogenesis.

5Apal, Taql, Fokl, and Bsml polymorphisms and the susceptibility of Behcet's disease: an updated meta-analysis.

The aim of this study was to investigate whether the gene polymorphisms of vitamin D receptor (VDR) had a genetic effect on the susceptibility of Behcet's disease (BD). We conducted a meta-analysis emphasizing the association between the VDR gene polymorphisms and the risk of BD. The strength of the association in five genetic models was assessed by pooled odds ratios (OR) with a corresponding 95%confidence interval (CI). A total of seven independent comparisons with 478 cases and 666 healthy controls were included in this meta-analysis. The overall results suggested that a significant association between ApaI polymorphism and BD risk was found in allele comparison, recessive model, and homozygote model among total populations. Subgroup analysis indicated that a significant association of ApaI polymorphism in the development of BD existed under the allelic model among Africans, while for Caucasians, a similar link was identified in the recessive model and homozygote model. Regarding Bsml polymorphism, an obvious relationship was detected to be significant in allele comparison and recessive model in the Caucasian population. Interestingly, the Fokl variant decreased the risk of BD in Africans under five genetic models, while it increased the risk in Caucasians across the recessive model and homozygote model. The results of this meta-analysis provide evidence of the link between the four widely studied polymorphisms in the VDR gene and BD, indicating a robust estimate of the genetic risk.

Clinical Utility of Amplification Refractory Mutation System-Based PCR and Mutation-Specific PCR for Precise and Rapid Genotyping of Angiotensin-Converting Enzyme 1 (ACE1-rs4646996 D>I) and Angiotensin-Converting Enzyme 2 (ACE2-rs4240157T>C) Gene Variations in Coronary Artery Disease and Their Strong Association with Its Disease Susceptibility and Progression

Background: Experimental clinical and research studies demonstrated that the renin–angiotensin system (RAS) affects the pathogenesis of atherosclerosis and the prognosis of coronary heart disease (CHD). The results show that ACE2 (angiotensin I-converting enzyme 2) might act as a protective protein for cardiovascular diseases; however, only a few studies in human populations have been carried out. The aim of this study was to develop, optimize, and validate a direct T-ARMS-based PCR assay for the precise and rapid genotyping of ACE1-rs4646996 D>I and ACE2-rs4240157T>C and study their association with coronary artery disease susceptibility and progression. Methodology: This study included 149 consecutive coronary artery disease patients and 150 healthy controls. We utilized T-ARMS for the precise and rapid genotyping of ACE2-rs4240157; rs4646994. Results: Our results indicated that the ACE1-rs4646996 D>I genotypes observed between CAD cases and controls were statistically significant (p < 0.008) and, similarly, the ACE2-rs4240157T>C genotypes observed were significant (p < 0.0001). Moreover, the frequency of the D allele (ACE1-D>I) and C allele (ACE2-rs4240157T>C) was found to be higher among CAD patients than the HC. Our results indicated that in the codominant model, the ACE2-ID genotype was strongly associated with increased CAD susceptibility in a codominant model with an OR of 2.37, (95%) CI = (1.023–5.504), and p < 0.04. Similarly, the ACE2-DD genotype was strongly associated with an increased CAD susceptibility with an OR of 3.48, (95%) CI = (1.49 to 8.117), and p < 0.003. Similarly, in allelic comparison, the D allele was strongly associated with CAD susceptibility with an OR of 1.59, (95%) CI = (1.12–2.24), and p < 0.003. Our results revealed that there was a significant correlation between ACE2-I/D genotypes and hypertension, T2D, and obesity (p < 0.05). The results of ACE2 rs4240157 genotyping indicated a strong association in the codominant model with an increased CAD susceptibility with an OR of 3.62, (95%) CI = (2.027 to 6.481), and p < 0.0001. Similarly, in a dominant inheritance model, a strong association is observed between the ACE2 rs4240157 (CT+CC) genotype with an OR of 6.34, (95%) CI = (3.741 to 10.749), and p < 0.0001. In allelic comparison, the T allele was strongly associated with CAD susceptibility with an OR of 5.56, (95% CI = (3.56 to 7.17), and p < 0.0001. Similarly, our results revealed that there was a significant association of the ACE2-rs4240157T>C genotypes with Triglycerides (mg/dL), HDL-C (mg/dL), total Cholesterol (mg/dL), and C-reactive protein (mg/L) in CAD. Conclusion: It was indicated that the ARMS technique and MS-PCR assay proved to be fast, accurate, and reliable for ACE2-rs4240157T>C and ACE1-rs4646996 D>I, respectively, and can be used as a potential molecular tool in the diagnosis of genetic diseases in undeveloped and developing countries—where there might be a shortage of medical resources and supplies. ACE1-I>D genotypes were strongly associated with T2D, hypertension, and obesity (p < 0.002). Besides the ACE2-rs4240157 CT heterozygosity genotype, the T allele was strongly associated with CAD susceptibility. Future longitudinal studies in different ethnic populations with larger sample sizes are recommended to validate these findings

MTRR rs1532268 polymorphism and gastric cancer risk: evidence from a meta-analysis.

ObjectiveThe methionine synthase reductase (MTRR) gene encodes the MTRR enzyme involved in the metabolic pathway of homocysteine. Several studies investigated the effect of the MTRR rs1532268 gene polymorphism on the risk of gastric cancer (GC), but the results have been inconsistent.MethodsWe performed a comprehensive and systematic search of PubMed, Google Scholar, MEDLINE, Science Direct, Scopus, CNKI, and Web of Science. Five studies were included in this meta-analysis to determine whether MTRR rs1532268 polymorphism contributes to the risk of GC.ResultsPooled data indicated that the MTRR rs1532268 polymorphism significantly increased GC risk under the allele comparison model (odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.01–1.29) and dominant model (OR = 1.14, 95% CI = 1.00–1.30). In the analysis stratified by ethnicity, no relationship was found in Whites or Asians.ConclusionOur meta-analysis suggests a positive correlation between MTRR rs1532268 polymorphism and GC development.

PSORS1 Locus Genotyping Profile in Psoriasis: A Pilot Case-Control Study.

(1) Background: The psoriasis susceptibility 1 (PSORS1) locus, located within the major histocompatibility complex, is one of the main genetic determinants for psoriasis, the genotyping profile for three single-nucleotide polymorphisms (SNPs) comprising the PSORS1 locus: rs1062470 within PSORS1C1/CDSN genes, rs887466 within PSORS1C3 gene, rs10484554 within LOC105375015 gene, were investigated and correlated with psoriasis risk and severity. (2) Methods: This pilot case-controlled study involved 100 psoriatic patients and 100 healthy individuals. We investigated three SNPs and assessed the relative gene expression profile for the PSORS1C1 gene. We then correlated the results with both disease risk and severity. (3) Results: The most significantly associated SNP in PSORS1 locus with psoriasis was rs10484554 with its C/T genotype 5.63 times more likely to develop psoriasis under codominant comparison. Furthermore, C/T and T/T genotypes were 5 times more likely to develop psoriasis. The T allele was 3 times more likely to develop psoriasis under allelic comparison. The relative gene expression of PSORS1C1 for psoriatic patients showed to be under-expressed compared to normal controls. (4) Conclusions: Our study revealed the association of the three studied SNPs with psoriasis risk and severity in an Egyptian cohort, indicating that rs10484554 could be the major key player in the PSORS1 locus.