GG Odds Ratios Research Articles

Association of β-fibrinogen polymorphisms and venous thromboembolism risk: A PRISMA-compliant meta-analysis.

Background:Venous thromboembolism (VTE) is a multifactorial disease in which genetic and acquired risk factors may contribute to disease pathogenesis. Several studies have demonstrated that β-fibrinogen (FGB) polymorphisms are associated with the risk of VTE. However, the results of these studies were not totally consistent. In this paper, we performed a meta-analysis to further investigate the relationship between FGB polymorphisms and susceptibility to VTE.Methods:To identify studies pertinent to the focused question, the following databases were systematically searched: PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, and Wanfang Data. The strength of correlations was evaluated by calculating pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). Subgroup analyses stratified by ethnicity, type of disorders, and source of control were also performed.Results:Overall, A total of 18 relevant case-control studies met the inclusion criteria and were incorporated in this meta-analysis, involving 3033 VTE cases and 4547 healthy controls. FGB -455G>A polymorphism and -148C>T polymorphism were not significantly associated with susceptibility to VTE in overall populations. However, results of stratified analysis demonstrated that among Caucasian population, the -455G>A mutation was negatively associated with the risk of VTE under all genetic comparison models (A:G OR = 0.80 95% CI = 0.70–0.91; GA + AA:GG OR = 0.80 95% CI = 0.68–0.93; GA:GG OR = 0.84 95% CI = 0.71–0.98; AA:GG + GA OR = 0.61 95% CI = 0.43–0.87; AA:GG OR = 0.57 95% CI = 0.40–0.82), which indicates FGB -455G>A polymorphism may be a protective factor for VTE. There was no correlation between -148C>T polymorphism and susceptibility to VTE in all subgroup analyses.Conclusion:FGB -455G>A polymorphism was associated with a decreased risk of VTE among the Caucasian population.

Genetic Variant Arg399Gln G>A of XRCC1 DNA Repair Gene Enhanced Cancer Risk Among Indian Population: Evidence from Meta-analysis and Trial Sequence Analyses.

The X-ray repair cross-complementation group 1 (XRCC1) gene plays an important role in base excision repair pathway. Several studies have reported contradictory results for XRCC1 exon 10 (Arg399Gln, G23990A, rs25487) gene polymorphism and cancer risk in Indian population, making it difficult to interpret them. Therefore, we have conducted a meta-analysis to evaluate the more precise association between XRCC1 exon 10 G>A gene polymorphism and risk of cancer by published studies. We searched PubMed (Medline) and Google scholar web databases to cover all studies published on association between XRCC1 exon 10 G>A gene polymorphism and cancer risk until August 2016. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to appraise the strength of association. Heterogeneity, publication bias and sensitivity analysis were also assessed. Twenty-five published studies had fulfilled the inclusion criteria comprising 4131 confirmed cancer cases and 5013 controls. When all studies were polled together, overall significant association was found between XRCC1 exon 10 G>A polymorphism and cancer risk in variant allele carrier (A vs. G: OR 1.217, 95% CI 1.056-1.402, p=0.007), homozygous (AA vs. GG: OR 1.359, 95% CI 1.036-1.783, p=0.027), dominant (AA+AG vs. GG OR 1.208, 95% CI 1.006-1.450, p=0.043) and recessive (AA vs. AG+GG: OR 1.315, 95% CI 1.029-1.680, p=0.029) genetic models. Further sensitivity analysis supported the stability of our result by showing similar ORs before and after removal of a single study. The present meta-analysis suggested that the XRCC1 exon 10 G>A polymorphism contribute cancer risk in Indian population, and supports that individuals with risk allele A and AA genotype are at higher risk of developing cancer.

The association between the LRRK2 R1628P variant and the risk of Parkinson’s disease in Asian: a meta-analysis

Many published case-control studies have investigated the association between Leucine-rich repeat kinase 2(LRRK2) R1628P and the susceptibility of Parkinson’s disease (PD). However, controversial results were obtained. Herein we performed this meta-analysis to assess the association between the LRRK2 R1628P variants and the risk of PD. Up to January of 2016, 5 databases were searched to identify case-control studies involving LRRK2 R1628P variants and PD risk. A total of 5736 PD patients and 4786 controls in 14 case-control studies were included in this meta-analysis. And STATA 12.0 statistics software was used to calculate available data from each study. The pooled odds ratios (OR) and 95% confidence interval (CI) were calculated to assess the genetic association between LRRK2 R1628P polymorphism and the risk of PD. The results indicated that LRRK2 R1628P variants were increased risk of PD when all studies were pooled (C vs. G OR=1.983, 95% CI 1.640-2.399; GC+CC vs. GG OR=1.971, 95% CI 1.625–2.391). Moreover, in the subgroup analysis by ethnicity, increased risks were identified among Chinese (GC+CC vs. GG, OR=1.96, 95% CI 1.60–2.41) as well as in non-Chinese Asian races (GC+CC vs. GG, OR=2.03, 95% CI 1.13–3.65). Therefore, our results suggest that the C allele, GC and CC genotype of LRRK2 R1628P variants contribute to the susceptibility of PD in Asian.

Effects of toll-like receptor 2 gene mutation on resistance to bovine brucellosis

Toll-like receptor 2 (TLR2) is an important pattern recognition receptor that play a pivotal role in the innate and adaptive immune systems. TLR2 has been identified as susceptibility loci for various infectious diseases. The aim of the present study was to investigate whether the functional genetic variations in TLR2 gene (T385G, G398A and C1828T) confer susceptibility or resistance to bovine brucellosis. The variants of TLR2 gene were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 511 Chinese Holstein cows (143 infected with brucellosis, 368 non-infected). For SNP T385G, genotypic frequency of GT and GG were significantly difference between brucella-infected and non-infected animals [p=0.0401 for both GT and GG; GT Odds Ratio (OR)=1.410 95% confidence interval (CI) (0.923–2.155); and GG OR=2.084 95% CI (1.116–3.893)]. Similarly, G allele showed significantly higher relative risk of brucellosis incidence than T allele [p=0.0064, OR=1.519 95% CI (1.123–2.053)]. The present study indicates that TLR2 gene could be a potential genetic marker for bovine brucellosis susceptibility.

Genetic polymorphisms in Glutathione S-transferase Omega (GSTO) and cancer risk: a meta-analysis of 20 studies.

Glutathione S-transferase Omega (GSTO) plays an important role in the development of cancer. Recently, a number of studies have investigated the association between single nucleotide polymorphisms on GSTO and susceptibility to cancer; however, the results remain inconclusive. We performed a meta-analysis of 20 studies, involving 4770 cases and 5701 controls to identify the strength of association by pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Overall, the pooled results revealed a significantly increased risk of susceptibility for GSTO2 polymorphism (GG vs. AA: OR = 1.20, 95%CI: 1.02–1.41, Pheterogeneity = 0.116), but no significant association was found for GSTO1 polymorphism. Subgroup analysis showed that GSTO2 polymorphism significantly increased cancer risk in Caucasian population (GG vs. AA: OR = 1.32, 95%CI 1.06–1.64, Pheterogeneity = 0.616) and GSTO2 polymorphism was significantly associated with elevated risk of breast cancer (GG vs. AA OR = 1.37, 95%CI: 1.06–1.77; Pheterogeneity = 0.281). This meta-analysis demonstrates that GSTO2 polymorphism may significantly increase cancer risk in Caucasian population and is associated with elevated risk of breast cancer; while GSTO1 polymorphism is not associated with cancer risk.

PS-004 Association Of The 45t > G Adiponectin Gene Polymorphism With Metabolic Syndrome In Egyptian Female Adolescents

Background Adiponectin gene (ADIPOQ) single nucleotide polymorphisms (SNPs) have been shown to influence adiponectin levels and have been associated with risk for obesity and insulin resistance (IR). However, these associations have not been fully examined in Egyptian adolescents. The aim of this study was to investigate the association of ADIPOQ gene 45T > G with risk of obesity and metabolic syndrome (MS) in Egyptian female adolescents. Methods The cross-sectional study was performed on 285 Egyptian female adolescents (mean age: 15.5 ± 2.3 and mean body mass index: 20.34 ± 5.67). Genotyping of adiponectin 45T > G polymorphism was detected by PCR-RFLP analysis. Anthropometric and biochemical parameters were measured by standard procedures. Insulin resistance was determined by the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Body fat was measured by Tanita Body Composition Analyzer. Results MS cases showed a higher distribution of TG and GG genotypes compared with cases without MS. Carriers of the mutated genotypes (TG+GG) exhibited higher levels of body mass index, body fat percentage, blood pressure, fasting insulin, fasting glucose, HOMA-IR, triglyceride, whereas lower levels of HDL-C and serum concentrations of adiponectin as compared with TT carriers. Association between MS and mutated genotypes of ADIPOQ gene 45T > G was observed (adjusted odds ratios (OR) = 3.65 for TG+GG carriers, OR = 2.25 for GG carriers and OR = 1.9 for G allele carriers). Conclusions The study suggests that adiponectin 45T > G polymorphism has a significant role in the development of MS in Egyptian female adolescents, possibly through an interaction with increase body weight and hypoadiponectinemia.

Association between APE1 T1349G polymorphism and prostate cancer risk: evidence from a meta-analysis.

APE1 T1349G polymorphism was considered to be associated with risk of cancer, but studies on the association between APE1 T1349G polymorphism and risk of prostate cancer remained inconclusive. A meta-analysis of published studies was performed to precisely assess the association between APE1 Asp148Glu polymorphism and prostate cancer risk. PubMed, Embase, and Wanfang databases were searched for published case-control studies investigating the association between APE1 T1349G polymorphism and prostate cancer risk. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were used to assess the strength of the association. Overall, seven studies with a total of 3,063 individuals were finally included into the meta-analysis. The heterogeneity analysis did not find obvious heterogeneity among those included studies. Meta-analysis of total seven studies did not find an obvious association between APE1 T1349G polymorphism and prostate cancer risk (G vs T OR (95 % CI) = 1.11 (0.99-1.24); GG vs TT OR (95 % CI) = 1.25 (0.96-1.62); TG vs TT OR (95 % CI) = 1.11 (0.95-1.30); GG/TG vs T OR (95 % CI) = 1.13 (0.97-1.32); GG vs TT/TG OR (95 % CI) = 1.16 (0.91-1.48)). Subgroup analyses by ethnicity showed that APE1 T1349G polymorphism was associated with increased risk of prostate cancer in Caucasians (G vs T OR (95 % CI) = 1.26 (1.02-1.56), P = 0.033; TG vs TT OR (95 % CI) = 1.44 (1.06-1.94), P = 0.019; GG/TG vs T OR (95 % CI) = 1.45 (1.08-1.94), P = 0.013). The meta-analysis suggests that APE1 T1349G polymorphism is associated with increased risk of prostate cancer, especially in Caucasians. More studies are needed to further identify the obvious association above.

Relationship between interleukin-10 -1082A/G polymorphism and risk of ischemic stroke: a meta-analysis.

ObjectiveTo analyze the association between −1082A/G polymorphism in interleukin-10 (IL-10) gene and ischemic stroke (IS) risk by meta-analysis.MethodsWe carried out a systematic electronic search in PubMed, BIOSIS Previews, Science Direct, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, Weipu database and WANGFANG Database. Pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to assess the strength of the association.Results7 studies were included. There was no significant association between IL-10 −1082A/G polymorphism and IS risk under all genetic models in overall estimates (A vs. G: OR = 1.23,95%CI = 0.85–1.79;AA vs. GG: OR = 1.01,95%CI = 0.47–2.19; AG vs. GG: OR = 0.76, 95%CI = 0.38–1.55; AA+AG vs. GG: OR = 0.89,95%CI = 0.46–1.73; AA vs. AG+GG: OR = 1.39, 95%CI = 0.91–2.13). Similarly, no associations were found in subgroup analysis based on ethnicity and source of controls. However, removing the study deviating from Hardy–Weinberg equilibrium (HWE) produced statistically significant associations for overall estimates under recessive model(AA VS. AG+GG OR 1.58, 95% CI 1.04–2.42) and among Asians in all genetic models (A VS.G OR 1.64, 95% CI 1.07–2.53; AA vs. GG OR1.91, 95% CI 1.31–2.80; AG vs. GG OR1.44, 95% CI 1.09–1.91; AA+AG vs. GG OR 1.54, 95% CI 1.18–2.01;AA VS. AG+GG OR 1.79, 95% CI 1.07–3.00). Even after Bonferroni correction, the associations were observed still significantly in Asians under the two models (AA vs. GG OR1.91, 95% CI 1.31–2.80, P = 0.0008; AA+AG vs. GG OR 1.54, 95% CI 1.18–2.01, P = 0.001).ConclusionThis meta-analysis indicates that IL10 −1082 A/G polymorphism is associated with IS susceptibility in Asians and the −1082 A allele may increase risk of IS in Asians. Considering the sample size is small and between-study heterogeneity is remarkable, more studies with subtle design are warranted in future.

Association between Tumor Necrosis Factor-α 308G/A Gene Polymorphism and Silicosis Susceptibility: A Meta-Analysis

BackgroundTumor necrosis factor-α (TNF-α) 308 G/A gene polymorphism has been reported to be associated with susceptibility to silicosis. However, the relevant study results are still inconsistent.Objective and MethodsA meta-analysis was performed in order to drive a more precise estimation of the relationship between TNF-α-308 G/A gene polymorphism and susceptibility to silicosis. Electronic databases were searched and nine separate studies were included. The pooled odds ratios (ORs) and the corresponding 95% confidence internal (CI) were calculated by a fixed effect model.ResultsA total of 1267 cases and 1214 controls were included. In the overall analysis, significantly increased silicosis risk was found (for GA+AA vs. GG OR=1.45, 95%CI: 1.20-1.760, P=1.58E4; for GA vs. GG: OR=1.53, 95%CI=1.25-1.86, P=3.11E5; for A allele vs. G allele: OR=1.27, 95%CI=1.08-1.50, P= 0.004). In the subgroup analysis, significantly increased silicosis risk was also found among Asians (for GA+AA vs. GG: OR=1.63, 95%CI=1.27-2.08, P=1.01E4), for GA vs. GG: OR=1.71, 95%CI=1.33-2.20, P=3.44E5), for A allele vs. G allele: OR=1.45, 95%CI=1.17-1.80, P=0.001). However, no significantly increased risk was found among non-Asians for all genetic models.ConclusionsTNF-α-308 G/A polymorphism might lead to an increased risk of silicosis susceptibility, especially for Asians. However, further studies with large sample sizes should be conducted to confirm the association.

Polymorphisms in the cytotoxic T-lymphocyte antigen 4 gene and acute rejection risk in transplant recipients

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene polymorphisms have been reported to influence the risk for acute rejection (AR) in transplant recipients. However, the results still remain controversial and ambiguous. The objective of the current study was to conduct a meta-analysis investigating the association between polymorphisms in the CTLA-4 gene and the risk of AR in transplant recipients. Electronic searches for all publications were conducted on associations between this variant and acute rejection in Medline and Embase databases through November 2011. Crude odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated to estimate the strength of the association. Three polymorphisms (+49 adenine/guanine [+49A/G], -318 cytosine/thymine [-318C/T], and the +6230G/A polymorphism [CT60]) in 18 case-control studies from ten articles were analyzed. This meta-analysis included 2,081 cases of transplant recipients in which 813 cases developed AR and 1,268 cases did not develop AR. The results indicated that there was no statistically significant association between the risk of AR and the +49A/G polymorphism or the -318C/T polymorphism (+49A/G: OR = 0.876, 95 % CI = 0.650-1.180 for GG vs. AA; OR = 1.121, 95 % CI = 0.911-1.379 for AG + GG vs. AA; -318C/T: OR = 0.397, 95 % CI = 0.138-1.143 for TT vs. CC; OR = 0.987, 95 %CI = 0.553-1.760 for CT + TT vs. CC). However, individuals who carried CT60 A allele might have a decreased risk of AR (AA vs. GG OR = 0.535, 95 % CI = 0.340-0.841, A vs. G OR = 0.759, 95 % CI = 0.612-0.914) in liver transplant recipients among Europeans, but because only two studies were included, so the result should be caution. In further stratified analyses for the +49A/G and the -318C/T polymorphisms, no obvious significant associations were found in subgroups of renal transplant recipients and Europeans, a reduced incidence of acute rejection was observed in liver transplant recipients that are homogenous for +49G (OR = 0.638, 95 % CI = 0.427-0.954 for GG vs. AA/AG), while this has not been observed in renal transplant recipients. Overall this meta-analysis suggests that +49A/G and the -318C/T polymorphisms in CTLA-4 may be not associated with the risk of rejection after organ transplantation, but CTLA +49A/G and +6230G/A polymorphisms may be associated with acute rejection after liver transplantation, not after renal transplantation. In future, more studies should be included to evaluate the association between +6230G/A polymorphism and AR risk.

The frequent UCP2 −866G>A polymorphism protects against insulin resistance and is associated with obesity: a study of obesity and related metabolic traits among 17 636 Danes

Uncoupling protein 2 (UCP2) is involved in regulating ATP synthesis, generation of reactive oxygen species and glucose-stimulated insulin secretion in β-cells. Polymorphisms in UCP2 may be associated with obesity and type 2 diabetes mellitus. To determine the influence of a functional UCP2 promoter polymorphism (-866G>A, rs659366) on obesity, type 2 diabetes and intermediary metabolic traits. Furthermore, to include these and previously published data in a meta-analysis of this variant with respect to its impact on obesity and type 2 diabetes. We genotyped UCP2 rs659366 in a total of 17 636 Danish individuals and established case-control studies of obese and non-obese subjects and of type 2 diabetic and glucose-tolerant subjects. Meta-analyses were made in own data set and in publicly available data sets. Quantitative traits relevant for obesity and type 2 diabetes were analysed within separate study populations. We found no consistent associations between the UCP2 -866G-allele and obesity or type 2 diabetes. Yet, a meta-analysis of data from 12 984 subjects showed an association with obesity (GA vs GG odds ratio (OR) (95% confidence interval (CI)): 0.894(0.826-0.968) P=0.00562, and AA vs GG OR(95% CI): 0.892(0.800-0.996), P=0.0415. Moreover, a meta-analysis for type 2 diabetes of 15 107 individuals showed no association. The -866G-allele was associated with elevated fasting serum insulin levels (P=0.002) and HOMA insulin resistance index (P=0.0007). Insulin sensitivity measured during intravenous glucose tolerance test in young Caucasian subjects (n=377) was decreased in carriers of the GG genotype (P=0.05). The UCP2 -866G-allele is associated with decreased insulin sensitivity in Danish subjects and is associated with obesity in a combined meta-analysis.

Association between CTLA-4 Exon-1 +49A>G Polymorphism and Primary Biliary Cirrhosis Risk: A Meta-analysis

CTLA-4 exon-1 +49A>G polymorphisms have been reported to influence the risk for primary biliary cirrhosis in many studies; however, the results still remain controversial and ambiguous. The aim of this study was to determine more precise estimations for the relationship between CTLA-4 exon-1 +49A>G polymorphisms and the risk for primary biliary cirrhosis. Electronic searches for all publications were conducted on associations between this variant and breast cancer in several databases through November 2010. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of the association. Eight studies were identified including 2151 cases and 2214 controls. Overall, there were no significant associations between CTLA +49G>A polymorphism and primary biliary cirrhosis risk (codominant model: GA vs. AA OR=1.190, 95% CI=0.818-1.732; GG vs. AA OR=1.153, 95% CI=0.858-1.550; dominant model: OR=1.181, 95% CI=0.873-1.599; and recessive model: OR=1.148; 95% CI=0.903-1.459). In the subgroup analysis by ethnicity, a significantly increased risk was found for Asians (GG vs. AA OR=1.873; 95% CI=1.202-2.921) and recessive model (OR=1.758; 95% CI = 1.271-2.433). In the stratified analysis by control sources, significant association were observed in population-based studies (GA vs. AA OR=1.432; 95% CI=1.078-1.902). This meta-analysis suggests that the CTLA-4 +49G>A polymorphism may be a risk factor for primary biliary cirrhosis in Asians.

Polymorphisms of Tumor Necrosis Factor-Alpha and Hepatocellular Carcinoma Risk: A HuGE Systematic Review and Meta-Analysis

Studies investigating the associations between tumor necrosis factor-alpha (TNFA) polymorphisms and hepatocellular carcinoma (HCC) risk report conflicting results. We conducted a meta-analysis to assess the association between TNFA gene TNFA-308(G/A), TNFA-238(G/A), TNFA-863(C/A), TNFA-857(C/T), TNFA-1031 (T/C) polymorphisms and HCC susceptibility. Two investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Database. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for TNFA polymorphisms and HCC were calculated in a fixed-effects model (the Mantel-Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate. This meta-analysis included 17 case-control studies, which included 2,357 HCC cases and 3,161 controls. Overall, the variant genotypes AA/AG of -308G/A were associated with a significantly increased HCC risk, when compared with GG genotype (AA vs. GG, OR=1.97, 95%CI=1.01-3.83; AG vs. GG, OR=1.88, 95%CI=1.23-2.88; AA/AG vs. GG, OR=1.80, 95%CI=1.19-2.72). When stratifying for ethnicity, significantly elevated HCC risk was found among Asians. Moreover, similar results were observed between TNFA-238G/A, TNFA-863C/A polymorphisms and HCC risk among Asians (for -238G/A, AG vs. GG OR=1.63, 95%CI=1.17-2.26, AA/AG vs. GG OR=1.61, 95%CI=1.16-2.24; for -863 C/A, AC vs. CC OR=1.72, 95%CI=1.03-2.88, AA/AC vs. CC OR=1.71, 95%CI=1.02-2.86), while no associations were observed between TNFA-857C/T, TNFA-1031T/C polymorphisms and HCC susceptibility. This meta-analysis shows that TNFA-308G/A, TNFA-238G/A and TNFA-863C/A polymorphisms may be associated with HCC among Asians. TNFA-857C/T and TNFA-1031T/C polymorphisms were not detected to be related to the risk for HCC.

Transporter associated with antigen processing 1 637A/G gene polymorphisms and susceptibility to nasopharyngeal carcinoma in Han population in Yunnan Province, China

To study the relationship between 637A/G gene polymorphisms of the transporter associated with antigen processing 1 gene and nasopharyngeal carcinomas (NPC) and to find out the susceptible genes of NPC in Han population in Yunnan Province, China. Two hundred and thirty-three cases with NPC and 296 cases matched cancer-free controls were genotyped for the TAP1 637A/G polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Epstein-Barr virus infection was detected by PCR. The adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated by using unconditional logistic regression model. Contrast with homozygous TAP1 637 AA, G allele significantly increasing risk of NPC was associated with homozygous 637 GG OR = 4.26 (95%CI were 2.08 - 8.66, P < 0.001) and heterozygous 637 AG OR = 1.56 (95%CI were 1.12 - 2.33, P < 0.05). The subjects at least having one TAP1 637 G allele had OR of 1.88 (95%CI were 1.35 - 2.82, P < 0.001). Furthermore, EBV infection may increase the risk of developing NPC interacting with TAP1 637 A/G polymorphism OR = 2.76(95% CI were 1.69 - 4.63, P < 0.001). The TAP1 637G allele is associated with the NPC in Han population in Yunnan China, EBV pathogenesis in NPC might be facilitated by polymorphisms in the TAP1 proteins.

No Association between hOGG1 Ser326Cys Polymorphism and Risk of Squamous Cell Carcinoma of the Head and Neck

No Association between <i>hOGG1</i> Ser326Cys Polymorphism and Risk of Squamous Cell Carcinoma of the Head and Neck