Allele Contrast Research Articles

Gene polymorphisms and risk of idiopathic pulmonary fibrosis: a systematic review and meta-analysis.

Idiopathic pulmonary fibrosis (IPF) has been widely hypothesized to occur as a result of an interplay between a nexus of environmental and genetic risk factors. However, not much is known about the genetic aspect of this disease. The objective of this review was to identify the genetic polymorphisms associated with the risk of developing IPF. We searched PubMed, EBSCO CINAHL Plus, Web of Science, and Wiley Cochrane Library databases for studies on risk factors of IPF published between March 2000 and November 2023. Studies with an IPF diagnosis based only on the American Thoracic Society and the European Respiratory Society guidelines were included. Thirty-one case-control studies were included with 3997 IPF and 20,925 non-IPF subjects. Two of the studies enrolled biopsy-proven IPF patients; 13 studies diagnosed IPF on the basis of clinical and high-resolution computed tomography (HRCT) findings; and 14 studies diagnosed based on both biopsy and clinical and HRCT findings. 16 studies with MUC5B rs35705950, IL-4 rs2243250, IL-4 rs2070874, and tumor necrosis factor α (TNFα)-308 were eligible for meta-analysis. The allele contrast model (T versus G) for MUC5B rs35705950 revealed statistically significant association of T allele with the risk of IPF [odds ratio (OR) 3.84, 95% confidence interval (CI) 3.20 to 4.61, adjusted p<0.0001), as was the allele contrast model for Asian (OR 2.83, 95% CI 1.51 to 5.32, adjusted p=0.009) and Caucasian (OR 4.11, 95% CI 3.56 to 4.75, adjusted p<0.0001). The allele contrast models for IL-4 rs2243250, IL-4 rs2070874, and TNFα-308 did not demonstrate any significant association with IPF. This review suggests an association of MUC5B rs35705950 T allele with the risk of developing IPF. To our knowledge, this study is the first to aggregate several genetic polymorphisms associated with IPF.

The 14-bp insertion/deletion as a promising gene polymorphism to understand cancer risk: Evidence from a systematic review and comprehensive meta-analysis

BackgroundHLA-G is associated with cancer cell escape. The 3’UTR polymorphism is involved in the regulation of membrane-bound HLA-G and soluble HLA-G proteins. The aim of our study was to assess the association of the HLA-G 14-bp insertion (I)/deletion (D) polymorphism with cancer susceptibility and its interaction with clinicopathological features and environmental factors. MethodsA meta-analysis was performed to investigate the association between the HLA-G 14-bp I/ D polymorphism and different types of cancers according to the Prisma guidelines. ResultsThirty-nine publications that studied the 14-bp I/D polymorphism in cancers met our inclusion criteria. The findings of the meta-analysis showed a significant association between the 14-bp I/D polymorphism and cancer risk under the allelic contrast model D vs. I (OR=1.112, 95% CI= 1.009-1.227, P = 0.033) suggesting that the D allele was a risk factor for cancer susceptibility. Stratification by cancer type demonstrated a significant association of the 14-bp I/D polymorphism with breast cancer under the D vs. I contrast allele model (OR=1.267, 95% CI= 1.028-1.563, P=0.027). No significant association was found for digestive, cervical, haematological and thyroid cancers. A comparison of groups stratified by ethnicity showed a significant association for Caucasians under the D vs. I model (OR=1.147, 95% CI= 1.002-1.313, P=0.047); and for mixed ethnicities under the DD+DI vs. II (OR=1.388, 95% CI= 1.083-1.780, P=0.010) and DI vs. II (OR= 1.402, 95% CI=1.077-1.824, P=0.012) models. A comparison of cancer risks associated with the 14-bp I/D polymorphism according to geographic location revealed significant risks for the D allele and DD genotype in North Africa, the Middle East and South America. However, no significant susceptibility to cancer associated with the 14-bp I/D polymorphism was shown for Europe and North Asia. The findings of a meta-analysis of subgroups by disease stage showed a significant association in both early and advanced stages, with the 14-bp deletion variant being a risk factor. Similarly, a significant cancer risk was shown for the 14-bp deletion variant in both low- and high-grade cancers. Finally, the risk associated with the 14-bp I/D polymorphism was higher in cancers with concomitant viral infection with human papillomavirus (HPV), hepatitis B virus (HBV) or hepatitis C virus (HCV). ConclusionThe findings of the overall meta-analysis showed a significant association between the HLA-G 14-bp I/D polymorphism and cancer susceptibility. The findings stratified analysis and subgroup comparisons showed that the 14-bp I/D deletion variant was associated with an increased risk of breast cancer. The HLA-G 14-bp I/D polymorphism may interact with individual and clinicopathological factors to alter cancer risk. These promising findings for cancer risk provide the basis for further studies that explore 14bp I/D polymorphism in cancer screening and immunotherapeutic approach.

Quantitative assessment of the associations between DNA repair gene XRCC3 Thr241Met polymorphism and pancreatic cancer

BackgroundPrior research exploring the correlation between the XRCC3 Thr241Met polymorphism and the susceptibility to pancreatic cancer has yielded conflicting outcomes. To date, there has been a notable absence of studies examining this polymorphism. The primary aim of the current investigation is to elucidate the potential role of the XRCC3 Thr241Met polymorphism as a risk factor in the development of pancreatic cancer.MethodsThe comprehensive literature search was meticulously conducted across primary databases, including PubMed, Embase, and CNKI (China National Knowledge Infrastructure), spanning from the inception of each database through January 2024. To synthesize the data, a meta-analysis was performed using either a fixed or random-effects model, as appropriate, to calculate the odds ratios (ORs) and their corresponding 95% confidence intervals (CIs).ResultsThe analysis revealed significant associations between the XRCC3 Thr241Met polymorphism and an increased risk of pancreatic cancer. This was evidenced through various genetic model comparisons: allele contrast (T vs. C: OR = 0.77, 95% CI = 0.70–0.86, P < 0.001), homozygote comparison (TT vs. CC: OR = 0.71, 95% CI = 0.58–0.88, P = 0.001), heterozygote comparison (TC vs. CC: OR = 0.67, 95% CI = 0.52–0.87, P = 0.003), and a dominant genetic model (TT/TC vs. CC: OR = 0.68, 95% CI = 0.57–0.81, P < 0.001). Additionally, subgroup analyses based on ethnicity disclosed that these associations were particularly pronounced in the Caucasian population, with all genetic models showing significance (P < 0.05).ConclusionsThe XRCC3 Thr241Met polymorphism has been identified as contributing to a reduced risk of pancreatic cancer in the Caucasian population. This finding underscores the need for further research to validate and expand upon our conclusions, emphasizing the urgency for continued investigations in this domain.

Tumor necrosis factor-α polymorphism and risk of primary nephrotic syndrome: A case-control study and meta-analysis.

The current study aims to explore the relationship between tumor necrosis factor-α (TNF-α) polymorphism and the risk of primary nephrotic syndrome (PNS). A total of 250 PNS patients were selected for this study, as well as 300 volunteers serving as the control group. TNF-α polymorphism were assessed using the polymerase chain reaction-restriction fragment length polymorphism method. In addition, a meta-analysis was conducted to analyze previously published literature on this topic. No significant differences were observed in the genotypes frequency or alleles frequency among the study populations. Meta-analysis results revealed a positive association between TNF-α rs1800629 polymorphism and allele contrast in African populations (p = 0), homozygote comparison (p = .007), heterozygote comparison (p = .026), recessive genetic model (p = .011), and dominant genetic model (p = .000). TNF-α rs1800629 polymorphism does not appear to confer any increased risk for PNS.

Association of vitamin D receptor genetic polymorphisms with the risk of infertility: a systematic review and meta-analysis

BackgroundThe causes of infertility have remained an important challenge. The relationship between VDR gene polymorphisms and infertility has been reported, with controversial findings.Objective and rationaleWe aimed to determine this relationship by conducting a systematic review and meta-analysis.Search methodsThe study was started with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) declaration and the final draft was registered as a protocol in PROSPERO (ID: CRD42023416535). The international electronic databases including PubMed (Medline), Scopus, Web of Sciences, and Cumulative Index to Nursing and Allied Health Literature (CINHAL) were searched until January 30, 2023, by using appropriate keywords. The quality of the final studies was assessed using the NOS Checklist for case–control studies. The odds ratios (ORs) for each of the genetic models were pooled, and a subgroup analysis based on geographical region and types of infertility was carried out by the MetaGenyo online tool.OutcomesCase–control studies including 18 and 2 studies about infertility in women and men, respectively, and 4 miscarriage studies were entered into the meta-analysis. The VDR gene TaqI polymorphism was associated with infertility susceptibility in women in the allele contrast [OR = 1.2065, 95% CI (1.0846–1.3421); P = 0.0005], Recessive model [OR = 1.3836, 95% CI (1.1197–1.7096); P = 0.002], Dominant model [OR = 1.2146, 95% CI (0.0484–1.4072); P = 0.009], Homozygote [OR = 1.4596, 95% CI (1.1627–1.8325); P = 0.001], and TT vs. Tt [OR = 1.2853, 95% CI (1.0249–1.6117); P = 0.029. ApaI and FokI gene polymorphisms were found to be significantly protective SNPs against women and men infertility in the Dominant model [OR = 0.8379, 95% CI (0.7039- 0.9975); P = 0.046] and Recessive model [OR = 0.421, 95% CI (0.1821–0.9767); P = 0.043], respectively. Sub-group meta-analysis showed a protection association of ApaI in dominant [OR = 0.7738, 95% CI = 0.6249–0.9580; P = 0.018] and AA vs. aa [OR = 0.7404, 95 CI% (0.5860–0.9353) P = 0.011725] models in PCOS subgroup, however, a negative association with idiopathic infertility was found in AA vs. Aa [OR = 1.7063, 95% CI (1.1039–2.6375); P = 0.016187] and Aa vs. aa [OR = 0.6069, 95% CI (0.3761–0.9792); P = 0.040754]. TaqI SNP was significantly associated with infertility in the African population and BsmI was associated with the disease mostly in the Asian population.ConclusionThis meta-analysis showed that the TaqI polymorphism may be linked to women’s infertility susceptibility. However, ApaI and FokI might be the protective SNPs against infertility in Women and men, respectively.

Associations Between Obesity-Related Gene MC4R rs17782313 Locus Polymorphism and Components of Metabolic Syndrome: A Systematic Review and Meta-Analysis.

Objective: It is well established that melanocortin-4 receptor (MC4R) rs17782313 locus polymorphism is associated with increased obesity risk and that obesity is strongly associated with an enhanced risk of all metabolic syndrome (MS) components. Thus, in this study, we examined the association between the MC4R rs17782313 locus polymorphism and the risk of the remaining MS components, namely, diabetes, hypertension, low high-density lipoprotein (HDL), and hypertriglyceridemia. Methods: We performed an extensive literature screening across six scientific databases, namely, PubMed, Embase, Web of Science, Medline, ScienceDirect, CNKI, and WanFang employing a specific search strategy. Eligible studies were selected for inclusion in our meta-analysis, and odds ratio (OR) values and 95% confidence interval (CI) were computed through fixed- or random-effects models to examine correlation strength. In addition, we performed subgroup analyses involving adjustment factors (unadjusted body mass index [BMI], adjusted BMI), race (Caucasian, Asian), and source of controls (population, hospital). Results: Twenty-two eligible studies were selected from 846 articles, involving 28,018 patients and 98,994 normal participants. Based on this meta-analysis, the MC4R rs17782313 locus polymorphism was associated with an augmented risk of diabetes (allele contrast model T vs. C: OR = 1.05, 95% CI = 1.03-1.08; dominant model TT vs. TC + CC: OR = 1.07, 95% CI = 1.03-1.11) and hypertension (dominant model TT vs. TC + CC: OR = 1.16, 95% CI = 1.03-1.31) risk. However, based on this analysis, the MC4R rs17782313 locus polymorphism was not associated with low HDL and hypertriglyceridemia risk. Conclusions: Based on this analysis, the MC4R rs17782313 locus polymorphism is associated with enhanced risks of diabetes and hypertension, while the associations with low HDL and hypertriglyceridemia require further exploration.

Genetic polymorphism of IL-18 influences susceptibility to lung cancer in population of eastern China.

The association of Interleukin-18 (IL-18) genetic polymorphism with lung cancer risk has yielded inconsistent findings in previous studies. The current research aims to clarify the relationship of IL-18 gene polymorphism with lung cancer susceptibility through experimental investigation and meta-analysis, providing insights for lung cancer prevention and treatment. We conducted a thorough search of major databases from their inception until March 2024. OR and 95%CI were calculated to know the results of meta-analysis. The IL-18 gene polymorphism was detected using the PCR-RFLP method. Significant associations were detected across all genetic models in allele contrast (A vs. C: Odds Ratio [OR] = 1.29, 95% Confidence Interval [CI] = 1.07-1.55, p = 0.006), homozygote comparison (AA vs. CC: OR = 1.87, 95%CI = 1.34-2.62, p < 0.001), recessive genetic model (AA vs. CT/CC: OR = 1.54, 95%CI = 1.08-2.20, p = 0.018), and dominant genetic model (AA/AC vs. CC: OR = 1.41, 95%CI = 1.12-1.78, p = 0.003). Three genotypes (AA, AC, and CC) were identified for the IL-18 -607 C/A polymorphism, with significant associations noted for the AA genotype and A allele (p = 0.018 and 0.005, respectively). This is the first study which investigates this polymorphism with lung cancer in population of eastern China. The IL-18 -607 C/A polymorphism appears to significantly increase the risk of lung cancer in the population of Eastern China. Further research is imperative to validate these findings.

Quantitative assessment of the association between TNF-α gene polymorphisms and angina risk.

Previous investigations into the correlation between tumor necrosis factor-α (TNF-α) gene polymorphism and susceptibility to angina have produced a range of results. This study aims to clarify the potential significance of TNF-α polymorphism as a contributing factor to the onset of angina. A comprehensive review of all corresponding literature was conducted across several major databases, covering their records from inception through to March 2024. Data were synthesized using meta-analysis techniques. Notable associations were identified in various genetic comparisons: allele contrast (A vs. G: OR=0.77, 95% CI=0.70-0.86, P<0.001), homozygote comparison (AA vs. GG: OR=3.35, 95% CI=2.51-4.48, P<0.001), heterozygote comparison (GA vs. GG: OR=1.69, 95% CI=1.19-2.40, P=0.003), recessive genetic model (AA vs. GG/GA: OR=2.40, 95% CI=1.91-3.03, P<0.001), and dominant genetic model (AA/GA vs. GG: OR=1.84, 95% CI=1.27-2.65, P=0.001). Furthermore, ethnicity-based subgroup analyzes revealed that these associations were especially significant within the Asian population and unstable angina, with all genetic models demonstrating statistical significance (P<0.05). TNF-α gene is significantly associated with an increased risk of angina, particularly among the Asian population and unstable angina. This finding underscores the importance of considering genetic factors in the assessment and management of angina risk.

A meta-analysis of the association between the ATIC 347 C/G polymorphism and methotrexate responsiveness and toxicity in rheumatoid arthritis

ObjectivesThe purpose of this study was to determine whether the 347 C/G polymorphism in the 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC) gene predicts the responsiveness to or toxicity of methotrexate (MTX) in patients with rheumatoid arthritis (RA). MethodTo identify relevant publications, we searched the Medline, Embase, Cochrane, and Web of Science databases. We performed a meta-analysis of studies on the relationship between the ATIC 347 C/G polymorphism and MTX toxicity or non-responsiveness in patients with RA. ResultsThirteen studies consisting of 3,185 patients with RA satisfied our inclusion criteria. The analysis included 10 studies on MTX responsiveness and seven studies on MTX toxicity in patients with RA in connection with ATIC 347C/G polymorphism. According to our meta-analysis, the ATIC 347 GG genotype and failure to respond to MTX treatment were significantly associated (OR = 0.741, 95% CI = 0.591–0.929, p=0.009). According to stratification by ethnicity, this genotype was significantly associated with non-responsiveness to MTX in Europeans (OR=0.548, 95% CI=0.377–0.796, p=0.002) but not in Asian populations (OR=0.882, 95% CI=0.665–1.1172, p=0.388). However, analyses employing allelic, dominant, and homozygous contrast models failed to detect any relationship between the polymorphism and the failure to respond to MXT. However, the ATIC 347GG genotype and MTX toxicity were not associated (OR=1.278, 95% CI=0.937–1.745, p=0.121). Asian and European populations showed no evidence of a relationship between the ATIC 347GG genotype and MTX toxicity (OR=1.252, 95% CI=0.905–1.732, p=0.175 and OR =1.617, 95% CI=0.549–4.765, p=0.383, respectively). ConclusionsThis meta-analysis revealed that ATIC 347 C/G polymorphism was related to non-responsiveness to MTX in European populations with RA. However, no significant correlation was found with MTX toxicity.

Frequency Evaluation of the Interleukin-6 -174G>C Polymorphism and Homeostatic Iron Regulator (HFE) Mutations as Disease Modifiers in Patients Affected by Systemic Lupus Erythematosus and Rheumatoid Arthritis.

Autoimmune diseases are generally characterized by a multifactorial etiology and are often associated with a genetic predisposition. Both iron metabolism and the inflammatory cytokine system have been shown to play a pivotal role in the dysregulation of the immune response in many different autoimmune conditions, rheumatologic diseases included. The purpose of this work was to analyze the frequency of mutations altering the expression of IL-6 or influencing iron metabolism in patients affected by autoimmune diseases such as Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE). In this study, 144 patients were enrolled: 77 and 67 patients were affected by RA and SLE, respectively. In these cohorts, the frequency of the IL-6 polymorphism -174G>C located in the IL-6 gene promoter was tested. Moreover, the frequencies of the three HFE gene variations associated with iron overload were analyzed: p.His63Asp, p.Ser65Cys and p.Cys282Tyr. The two mutations p.His63Asp and p.Ser65Cys in the HFE gene did not reach statistical significance in any of the comparisons, regardless of the statistical model, cohorts of patients and control populations analyzed. The frequencies of the p.Cys282Tyr mutation and the IL-6 polymorphism -174G>C were found to be overall significantly decreased in RA and SLE patients when the Dominant model and Allele contrast were adopted with both the Odds Ratio and Chi-square. Although further investigation is needed, the examination of the frequencies of the -174G>C IL-6 promoter polymorphism and HFE mutations may add some valuable information on the interplay linking iron metabolism, inflammation and immunity in autoimmune diseases such as SLE and RA.

Association of vitamin D receptor gene polymorphism with the risk of sepsis: A systematic review and meta-analysis.

To investigate the association between sepsis and the vitamin D receptor (VDR) gene polymorphisms. Databases including PubMed, Cochrane Library, EMbase, CNKI, Wanfang Data, and VIP Data were systematically searched. The association was assessed using odds ratios (ORs), and 95% confidence intervals (CIs). The statistical tests were performed using Review Manager 5.4. We identified a total of 5 studies. The relationship between VDR gene polymorphisms (Apa I, Bsm I, Taq I, and Fok I), and incidence of sepsis was investigated. The results of this meta-analysis showed that the allelic contrast model (F vs f, P = .03, OR = 0.65, 95% CI = 0.44-0.95), dominant genetic model (FF vs Ff + ff, P = .02, OR = 0.53, 95% CI = 0.30-0.91), and codominance genetic model (FF vs ff, P = .03, OR = 0.39, 95% CI = 0.16-0.91) of VDR Fok I locus increased the risk of sepsis, and the lack of association between the VDR Fok I gene polymorphism and the risk assessment of sepsis, based on the ethnic subgroup analysis, might be attributable to the small sample size. The risk of sepsis with Apa I, Bsm I, and Taq I did not appear to be correlated. This meta-analysis revealed that the VDR Fok I polymorphism is closely associated with the susceptibility to sepsis, and patients with sepsis have lower 25-hydroxyvitamin D levels. VDR Fok I gene mutations may change the risk of sepsis.

The role of NLRP3 and CARD8 polymorphisms in the risk of rheumatoid arthritis: A meta-analysis of genetic association studies.

To investigate the potential associations between rheumatoid arthritis (RA) and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) rs35829419, rs10754558, s4612666, and caspase recruitment domain family member 8 (CARD8) rs2043211 polymorphisms. Relevant papers were searched for in MEDLINE, Embase, and Web of Science. Allele contrast, recessive, dominant, and homozygote contrast models were used to investigate the relationship between the NLRP3 rs35829419, rs10754558, and s4612666, and CARD8 rs2043211 polymorphisms and RA. This review was registered with PROSPERO (CRD42023451231). The meta-analysis included 11 comparative studies comprising 3789 patients with RA and 3956 controls. No significant association was found between NLRP3 rs35829419 C allele and RA in Europeans, Arabs, or Latinos. The NLRP3 rs10754558 G allele was not associated with RA in the Asian or Arab populations. However, a single study in Latin America discovered a link between RA and the NLRP3 rs10754558 G allele. The NLRP3 rs4612666 T allele was not associated with RA, according to the meta-analysis. When ethnicity was stratified, there was no association between the NLRP3 rs4612666 T allele and RA, except for a single study that found an association among Arabs. The CARD8 rs2043211 T allele did not seem to be associated with RA. According to an ethnic stratification study, the CARD8 rs2043211 T allele did not appear to be associated with RA in Europeans, Arabs, or Latinos. The meta-analysis indicated that the NLRP3 rs35829419, rs10754558, and s4612666 polymorphisms, as well as the CARD8 rs2043211 polymorphism, were not linked to RA susceptibility.

Association of VEGF-116G/A Promoter Polymorphism with Esophageal Cancer Risk: A Case-Control study and an Updated Meta-Analysis on Gastrointestinal Tract Cancers.

The present study aimed to investigate the potential association of VEGF-116G/A promoter polymorphism with esophageal cancer risk in North-West Indians and to perform a comprehensive meta-analysis of VEGF-116G/A polymorphism in Gastrointestinal Tract (GIT) cancers. A total of 679 DNA samples (333 esophageal cancer patients and 346 healthy controls) were genotyped for VEGF-116G/A polymorphism using Sanger sequencing. In silico analysis was carried out to predict the impact of VEGF-116G/A polymorphism on transcription factor binding sites. Ten studies including 2157 patients and 2307 controls on different GIT cancers were included in the meta-analysis. Results: The AA genotype and A allele of VEGF -116G/A polymorphism was significantly associated with an increased risk of esophageal cancer. In silico analysis predicted that A allele of VEGF-116G/A polymorphism created new binding sites for STAT4, c-Ets-1 and Elk-1 transcription factors. The meta-analysis results showed that VEGF-116G/A polymorphism was associated with an increased risk of GIT cancer under the recessive and AA vs GG genetic model in the overall population. Stratification of the studies by ethnicity revealed an increased risk of GIT cancers in Asians under allele contrast, recessive, AA vs GG and AA vs AG model. Analysis based on cancer type revealed an increased risk of esophageal cancer under allele contrast, recessive, AA vs GG and AA vs AG comparison model and increased risk of oral cancer was observed under the allele contrast model and dominant model. VEGF-116G/A polymorphism was associated with esophageal cancer risk in North- West Indians. The findings of the present meta-analysis showed a significant association of VEGF-116G/A polymorphism with GIT cancer risk.

CYP17A1 (rs74357) polymorphism and polycystic ovary syndrome risk: a systemic review and meta-analysis.

To investigate the association between CYP17A1 (rs74357) polymorphism and the risk of Polycystic Ovary Syndrome (PCOS). Literature on the association of CYP17rs74357 gene polymorphism and susceptibility to PCOS was retrieved by searching databases such as PubMed, Science Direct, Google Scholar and Embase from. The association measure was analyzed using an Odds Ratio (OR) and 95% Confidence Interval (CI). All the statistical analyses were executed using CMA 3.0 Software. In the present meta-analysis,24 studies including 3462 PCOS and 2898 controls were analyzed. The overall results validated that the 17 CYP17 T/C (rs74357) gene polymorphism was significantly associated with PCOS risk in 5 genetic models: recessive model (fixed and random effect), dominant model (random effect), CC vs. TT (fixed effect), CT vs. TT (fixed effect), and allele contrast (random effect). Stratified analyses by ethnicity/country also detected significant association between Asian and Caucasian under the recessive, dominant, CC vs. TT, CC vs. CT, and the allele contrast models. In the present study, CYP17 T/C (rs74357) gene polymorphism increase the susceptibility of PCOS, and the recessive C allele, can be proposed as a predictive factor for the risk of PCOS or an important pathway in PCOS associated metabolic and hormonal dysregulation especially insulin resistance.However, larger sample size andmultiracial studies are needed in the future to confirm the findings.

ENOS polymorphisms on male infertility: An updated systematic review and meta-analysis.

This meta-analysis was performed to examine the association of 3 endothelial nitric oxide synthase (eNOS) gene polymorphisms with male infertility. The literature on the relation between the mutant of eNOS and male infertility before July 1, 2022, was conducted in Pubmed, Medline, and Web of Science. The search strategy is as follows: (eNOS OR ECNOS OR nitric oxide synthase 3 OR NOS3) AND (polymorphism OR mutation OR variation OR SNP OR genotype) AND (male infertility). Statistical analysis was performed with the web of MetaGenyo, Stata 12, trial sequential analysis 0.9Beta, and the web of GTEx. Overall, 13 studies (26 case-controls) were included involving 6518 cases and 5461 controls for 3 polymorphisms (rs2070744, rs1799983, rs61722009) of eNOS. We found that eNOS rs2070744 was correlated with an increased risk of male infertility (C vs. T: odds ratio [OR], 1.48; 95% confidence interval [CI], [1.19-1.85]; CC vs. TT: OR, 2.59; 95% CI, [1.40-4.80]; CT vs. TT: OR, 1.17; 95% CI, [1.00-1.38]; CC vs. CT + TT: OR, 2.50; 95% CI, [1.35-4.62]; CC + CT vs. TT: OR, 1.41; 95% CI, [1.21-1.64]). And eNOS rs1799983 was correlated with an increased risk of male infertility (allele contrast T vs. G: OR, 1.41; 95% CI, [1.01-1.96]; P = .043; recessive model TT vs. TG + GG: OR, 2.00; 95% CI, [1.03-3.90]; P = .042). In the stratified analysis of rs61722009, we found Asians might be correlated with an increased risk of male infertility (4a vs. 4b: OR, 1.50; 95% CI, [0.94-2.38]; 4a4a vs. 4b4b: OR, 2.56; 95% CI, [0.70-9.38]; 4a4b vs. 4b4b: OR, 1.36; 95% CI, [0.87-2.13]; 4a4a vs. 4a4b + 4b4b: OR, 2.57; 95% CI, [0.91-7.30]; 4a4a + 4a4b vs. 4b4b: OR, 1.44; 95% CI, [0.87-2.40]). The eNOS rs2070744 polymorphism and rs1799983 are associated with the risk of male infertility, and rs61722009 might be a risk factor for Asians.

Systemic review and meta-analysis of the association between interleukin-10 and Takayasu arteritis.

The aim of this meta-analysis is to investigate the relationship between interleukin (IL)-10 levels and its polymorphism and Takayasu arteritis (TAK). Five databases including PubMed, Web of Science, Ovid, Sinomed and China National Knowledge Infrastructure (CNKI) were gone through from inception to March 31, 2022. Studies were screened according to the inclusion and exclusion criteria. Newcastle-Ottawa Scale (NOS) was applied to assess study quality. Strengths of association were evaluated by odds ratio (OR) and 95% CI. The T v. t (allele contrast), TT v. tt (homozygous contrast), Tt vs tt (heterozygous contrast), TT + Tt vs tt (dominant contrast) and TT vs Tt + tt (recessive contrast) models were adopted. Seven studies were included. No significant relationship between IL-10 and TAK was detected in the included patients (P > 0.05). The levels of IL-10 were lower in the active group than those in the stable group, which was -0.47 (95% CI: -0.93, 0.00) (P = 0.05). No significant relationships between IL-10 and TAK were found under all contrasts for polymorphisms rs1800871, rs1800872 and rs1800896 (P > 0.05). There was no significant difference in IL-10 levels between TAK patients and control subjects. The levels of IL-10 were lower in TAK patients in the active stage. There was no significant association between IL-10 gene polymorphisms and TAK. Further well-designed studies with larger sample sizes in patients with different stages are needed.

Evaluation of the Relationship Between Dopamine Receptor D2 Gene TaqIA1 Polymorphism and Alcohol Dependence Risk.

Several studies are published, that investigated dopamine receptor 2 (DRD2) gene TaqIA polymorphism as a risk factor for alcohol dependence (AD) with positive and negative associations. To derive a more precise estimation of the relationship, a meta-analysis of case-control studies that examined the association between DRD2 gene Taq1A polymorphism and alcohol dependence was performed. Eligible articles were identified through a search of databases including PubMed, Science Direct, Springer link, and Google Scholar. The association between the DRD2 TaqIA polymorphism and AD susceptibility was conducted using odds ratios (ORs) and 95% confidence intervals (95% CIs) as association measures. A total of 69 studies with 9125 cases and 9123 healthy controls were included in the current meta-analysis. Results of the present analysis showed significant association between DRD2 TaqIA polymorphism and AD risk using five genetic modes (allele contrast model-OR 1.22, 95% CI 1.13-1.32, p < 0.0001; homozygote model-OR 1.35, 95%CI 1.18-1.55; p ≤ 0.0001; dominant model-OR 1.29; 95% CI 1.20-1.39; p < 0.0001; recessive model-OR 1.21; 95% CI 1.08-1.36; p = 0.0006). There was no significant association found in subgroup analysis, TaqIA polymorphism was not significantly associated with AD risk in the Asian population under all genetic models, but in the Caucasian population, TaqIA polymorphism was significantly associated with AD risk. Overall, results support the hypothesis that DRD2 Taq1A polymorphism plays a role in alcohol dependence.

Systemic assessment of solute carrier family 11-member A1 (rs17235409) gene polymorphism and Mycobacterium Tuberculosis Risk in Asian and caucasian population: A comprehensive updated meta-analysis.

The present meta-analysis was assessed to confirm the association between solute carrier family 11-member A1 (SLC11A1) gene (rs17235409) polymorphism with the Mycobacterium tuberculosis infection in the Asian and Caucasian populations. A search was conducted using the databases including Google Scholar, Science Direct, Embase, and PubMed to find the case-control studies related to SLC11A1 gene polymorphism and tuberculosis (TB) infection. The MetaGenyo programme was used to perform statistical analyses of the data. The odds ratio and 95% confidence interval were calculated based on genetic models such as allelic model, dominant model, recessive model, and overdominant. The heterogeneity and publication bias for the present study were examined to assess its quality. The study was registered in PROSPERO (ID Number: 461434). This current study revealed the association between the SLC11A1 gene polymorphism with TB. The statistical value obtained at P < 0.05 was deemed to be statistically significant. The meta-analysis results revealed that allele contrast and recessive models are significant association between SLC11A1 gene polymorphism with risk of TB infections, and dominant and overdominant models have no significant association with TB risk. In addition, the subgroup analysis based on the ethnicity dominant revealed a significant association with the risk of TB. Therefore, this results that the gene SLC11A1 has a significant association for allelic and recessive and has no significant association for dominant and overdominant with the risk of TB. According to the data retrieved from the database with respect to the present study revealed that SLC11A1 gene polymorphism rs17235409 for allelic, recessive models have been associated with TB infections, but dominant and overdominant models have not been associated with TB infections.

Associations between interleukin 17A and 17F polymorphisms and asthma susceptibility: A meta-analysis.

Owing to their role in inflammatory reactions and immunological responses as well as their chromosomal location, interleukin (IL) 17A and 17F are regarded as candidate causal genes associated with asthma. The aim of this study was to determine whether IL17 polymorphisms are associated with susceptibility to asthma. We used the PubMed/Medline and Embase databases to search for studies reporting IL17 polymorphisms in patients with asthma and healthy controls. Meta-analyses were conducted to determine the associations between IL17A rs8193036 (-737C/T), rs2275913 (-197G/A), rs3819024 (A/G), rs3748067 (C/T), and rs4711998 (A/G) and IL17F rs763780 (7488A/G), rs2397084 (T/C), rs1889570 (C/T), rs11465553 (G/A), and rs1266828 (T/C) polymorphisms and asthma susceptibility. A total of 20 studies were included in this meta-analysis. Our results revealed the IL17A rs8193036 CC genotype was associated with asthma susceptibility (odds ratio [OR]=1.490, 95% confidence interval [CI]=1.027-2.161, p=.036). However, stratification by ethnicity indicated no association between this polymorphism and asthma in European and Asian subjects. Furthermore, no association was found between this polymorphism and asthma using the allele contrast, dominant or homozygous contrast models. No evidence of an association was found between any of the other IL17A and IL17F polymorphisms and asthma susceptibility in this meta-analysis. This meta-analysis showed that, among the studied polymorphisms, only the CC genotype of IL17A rs8193036 is associated with asthma susceptibility.

MTNR1B rs1387153 Polymorphism and Risk of Gestational Diabetes Mellitus: Meta-Analysis and Trial Sequential Analysis

Background: Published data on the association between the MTNR1B rs1387153 polymorphism and gestational diabetes mellitus (GDM) risk are controversial. Objective: A meta-analysis was performed to assess whether the polymorphism of MTNR1B rs1387153 is associated with GDM risk. Method: Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Databases were searched to identify eligible studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for MTNR1B rs1387153 polymorphism and GDM were appropriately derived from fixed-effects or random effects models. Results: A total of 8 studies were enrolled in this meta-analysis. The pooled analyses revealed that MTNR1B rs1387153 polymorphism significantly increased the risk of GDM in all models (allele contrast (C vs. T): OR, 0.78; 95% CI, 0.73–0.83; homozygote (CC vs. TT): OR, 0.61; 95% CI, 0.53–0.69; heterozygote (CT vs. TT): OR, 0.78; 95% CI, 0.69–0.89; dominant model (CC + CT vs. TT): OR, 0.71; 95% CI, 0.63–0.80; recessive model (CC vs. CT + TT): OR, 0.73; 95% CI, 0.67–0.81). Further subgroup analyses by ethnicity of participants yielded similar positive results. Conclusions: Present meta-analysis reveals that MTNR1B rs1387153 variant may serve as genetic biomarkers of GDM.