The CTLA-4 +49 A/G and ?318 C/T polymorphisms and susceptibility to asthma: a meta-analysis

The aim of this study was to explore whether cytotoxic T lymphocyte antigen-4 (CTLA-4) +49 A/G, and -318 C/T polymorphisms confer susceptibility to asthma. A meta-analysis was conducted on the associations between the CTLA-4 +49 A/G, and -318 C/T polymorphisms and asthma using; (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) the additive model. Eight studies on the CTLA-4 polymorphisms and asthma involving 2,330 patients with asthma and 1,743 control subjects were included in this meta-analysis. The meta-analysis revealed an association between asthma and the CTLA-4 +49 A/G polymorphism under the dominant model in Asians (OR = 0.758, 95 % CI = 0.599-0.958, p = 0.020). Stratification by age indicated an association between the CTLA-4 +49 GG+GA genotype and asthma in children (OR = 0.690, 95 % CI = 0.497-0.957, p = 0.026), but not in adults (OR = 0.837, 95 % CI = 0.598-1.172, p = 0.300). Furthermore, stratification by atopy status indicated an association between the CTLA-4 +49 G allele and atopic asthma (OR = 0.639, 95 % CI = 0.464-0.881, p = 0.006), but not non-atopic asthma (OR = 0.706, 95 % CI = 0.385-1.294, p = 0.266). There was no association between asthma and the CTLA-4 -318 C/T polymorphism for the whole population, or when stratified by ethnicity, age, or atopy status. This meta-analysis demonstrates that the CTLA-4 +49 A/G polymorphism confers susceptibility to asthma in Asians, children, patients with atopy status, but there was no association between the CTLA-4 -318 C/T polymorphism and asthma susceptibility.     

Association between CTLA-4 exon-1 +49A/G polymorphism and systemic lupus erythematosus: an updated analysis

The results of studies on association between CTLA-4 exon-1 +49A/G (rs231775) polymorphism and susceptibility to systemic lupus erythematosus are controversial. To derive a more precise estimation of the relationship between the CTLA-4 exon-1 +49A/G polymorphism and SLE, a meta-analysis of 18 published case-control studies was performed. 18 studies meeting our inclusion criteria comprising 1806 SLE cases and 2,490 controls were included. The effect summary odds ratio (OR) and 95 % confidence intervals were obtained. Publication bias was tested by funnel plot, Egger's test and heterogeneity was assessed. The combined results showed that there were significant differences in genotype distribution between SLE cases and control on the basis of all studies, GG versus AA (OR = 1.53, 95 % CI: 1.12-2.10), GG versus GA/AA (OR = 1.30, 95 % CI: 1.04-1.64), GG versus GA (OR = 1.27, 95 % CI: 1.03-1.55). When stratifying for the race, the phenomenon was found that SLE cases had a significantly higher frequency of GG/GA versus AA (OR = 1.58, 95 % CI: 1.23-2.03), GG versus AA (OR = 1.89, 95 % CI: 1.23-2.91), GG versus GA/AA(OR = 1.39, 95 % CI: 1.03-1.89), GA versus AA(OR = 1.38, 95 % CI: 1.06-1.80) and G versus A(OR = 1.34, 95 % CI: 1.07-1.67) than control in Asians. Our meta-analysis results suggest that CTLA-4 exon-1 +49A/G polymorphism might be a risk factor for SLE susceptibility, at least in Asians. The large sample and well-designed study based on different ethnic groups should be considered in future associated studies to clarify the association of CTLA-4 exon-1 +49A/G polymorphism with SLE susceptibility.     

CTLA-4 polymorphisms and susceptibility to Behcet’s disease: a meta-analysis

The aim of this study was to explore whether cytotoxic T lymphocyte antigen-4 (CTLA-4) polymorphisms confer susceptibility to Behcet's disease (BD). A meta-analysis was conducted on the associations between the CTLA-4 +49 A/G, -318 C/T, CT60 A/G polymorphisms and BD using; (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) the additive model. A total of 8 separate comparison studies on BD were considered in the meta-analysis. Meta-analysis of the CTLA-4 +49 A/G polymorphisms showed no association between BD and the CTLA-4 +49 G allele in all study subjects (odds ratio [OR] = 0.780, 95 % confidence interval [CI] = 0.491-1.240, p = 0.294). Moreover, stratification by ethnicity indicated no association between the CTLA-4 +49 G allele and BD in Turkish population. No association was found between BD and the CTLA-4 +49 A/G polymorphisms using recessive or dominant models or contrast of homozygotes. No association was found between BD and the CTLA-4 -318 C/T or CT60 A/G polymorphisms. This meta-analysis showed that no association was found between CTLA-4 +49 A/G, -318 C/T or CT60 A/G polymorphisms and BD.     

Cytotoxic T-lymphocyte antigen-4 polymorphisms and susceptibility to osteosarcoma

Despite the knowledge of many genetic alterations present in osteosarcoma, the complexity of this disease precludes placing its biology into a simple conceptual framework. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) plays important roles in downregulating T-cell activation, thereby attenuating anti-tumor responses and increasing cancer susceptibility. Polymorphisms in the CTLA-4 gene are associated with different autoimmune diseases and cancers. The current study evaluated the association of four CTLA-4 gene mutations, -1661A/G (rs4553808), -318C/T (rs5742909), +49G/A (rs231775), and CT60A/G (rs3087243), with osteosarcoma in the Chinese population. CTLA-4 polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism in 267 osteosarcoma patients and 282 age-matched healthy controls. Results showed that the CTLA-4 gene +49 AA genotype, +49 A allele, and GTAG haplotype were significantly more frequent in osteosarcoma patients than in controls (odds ratio [OR] 2.20, 95% confidence interval [CI] 1.23-2.95, p?=?0.007; OR 1.32, 95% CI 1.03-1.69, p?=?0.029, and OR?=?1.47, 95% CI 1.03-2.09, p?=?0.033, respectively). The CTLA-4 +49G/A polymorphism and GTAG haplotype are associated with increased risk of osteosarcoma.     

Meta-analysis of epidermal growth factor polymorphisms and cancer risk: involving 9,779 cases and 15,932 controls

The epidermal growth factor (EGF) pathway stimulates proliferation and differentiation of epidermal and epithelial tissues, and plays an important role in tumorigenesis. The association between EGF polymorphisms and cancer risk is controversial; thus, we performed this meta-analysis. Overall, 41 case-control studies with 9,779 cases and 15,932 controls were retrieved. We found that EGF +61A/G polymorphism increased overall cancer risk (G allele vs. A allele: OR=1.181, 95% CI=1.077-1.295, P(heterogeneity) < 0.001; GG vs. AA: OR=1.370, 95% CI=1.143-1.641, P(heterogeneity) < 0.001; GG+GA vs. AA: OR=1.175, 95% CI=1.047-1.318, P(heterogeneity) < 0.001). In the stratified analysis by cancer type, the +61?G allele was a risk factor for colorectal cancer, esophageal carcinoma, gastric cancer, and hepatocellular carcinoma. Individuals who carried +61G allele had higher cancer susceptibility in mixed and European racial subgroups. An increased association was detected in the hospital-based subgroup. No significant association was found among EGF -1380A/G, -1744G/A, rs6983267T/G polymorphisms and cancer risk.     

CTLA-4 exon 1 +49 polymorphism alone and in a haplotype with ?318 promoter polymorphism may confer susceptibility to chronic HBV infection in Chinese Han patients

Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) plays a pivotal role in regulating T cell activation, which is believably critical for the outcome of hepatitis B virus (HBV) infection. The expression and function of CTLA-4 may be affected by gene polymorphisms. This study investigated the influence of CTLA-4 polymorphisms on disease susceptibility in Chinese Han patients with chronic HBV infection. CTLA-4 +49A/G and -318C/T polymorphisms were evaluated by DNA amplification with polymerase chain reaction followed by the restriction fragment length polymorphism analysis. The patients with chronic HBV infection had higher frequencies of genotype AA and allele A of CTLA-4 +49A/G polymorphism. The haplotype +49A-318C was significantly over-represented (P < 0.001) and haplotype +49G-318C under-represented (P = 0.006) in the patients. The +49GG genotype was more frequent (P = 0.009) and +49A allele was less frequent in patients with lower ALT levels (P = 0.012) in HBeAg positive chronic hepatitis B. It is indicated that CTLA-4 +49A/G polymorphism alone and in a haplotype with -318C allele may confer susceptibility to chronic HBV infection in Chinese Han patients.     

Lack of Association between Interleukin-10 Gene Polymorphisms and Graft Rejection Risk in Kidney Transplantation Recipients: A Meta-Analysis

Background

Interleukin-10 (IL-10) is an important immunomodulatory cytokine. Several studies focused the association between IL-10 promoter gene polymorphisms and graft rejection risk in kidney transplantation recipients. However, the results of these studies remain inconclusive. The aim of this study was to conduct a meta-analysis to further assess the associations.

Methods

The PubMed, Embase, and Ovid Medline databases were searched. Two independent authors extracted data, and the effects were estimated from an odds ratio (OR) with 95% confidence intervals (CIs). Subgroup and sensitivity analyses identified sources of heterogeneity.

Results

A total of 16 studies including 595 rejection patients and 1239 stable graft patients were included in order to study the IL-10 -1082 (rs1800896 G/A), -819 (rs1800871 C/T), -592 (rs1800872 C/A) and IL-10 (-1082,-819,-592) polymorphisms. The -1082 G/A polymorphism was not associated with an increased graft rejection risk (OR = 1.03; 95%CI, 0.85–1.25, P = 0.74 for GA+AA vs. GG model). Moreover, all of the -819 C/T (OR = 1.06, 95%CI, 0.79–1.42, P = 0.70 for TA+TT vs. CC model), -592 C/A (OR = 1.10, 95% CI, 0.85–1.42, P = 0.47 for AC+AA vs. CC model) and IL-10 (-1082,-819,-592) polymorphisms (OR = 1.00, 95%CI, 0.79–1.27, P = 0.98 for I+L vs. H model) did not increase the graft rejection risk. In addition, we also performed subgroup analysis by ethnic group (mainly in Europeans or Asians) and rejection type (acute or chronic). There was also lack of evidence of a significant association between the IL-10 gene polymorphism and graft rejection risk. The present meta-analysis indicated that the IL-10 gene polymorphism was not associated with graft rejection risk in kidney transplantation recipients.

Conclusion

This meta-analysis found evidence that the IL-10 polymorphism does not increase the risk of graft rejection in kidney transplantation recipients. Further chronic rejection and other ethnic population studies are needed to confirm our results.     

Cytotoxic T-lymphocyte antigen-4 +49G/A polymorphism and susceptibility to pancreatic cancer

Although pancreatic cancer has been extensively studied, few risk factors have been identified. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) plays important roles in downregulating T-cell activation, thereby attenuating antitumor responses and increasing cancer susceptibility. The CTLA-4 gene +49G/A polymorphism (rs231775) has been reported to be associated with various cancers. The current study evaluated the association of the CTLA-4 gene +49G/A polymorphism with pancreatic cancer in the Chinese population. Six hundred and two pancreatic cancer patients and 651 healthy controls were investigated for CTLA-4 +49G/A polymorphism by polymerase chain reaction-restriction fragment length polymorphism analysis. Data showed that prevalence of CTLA-4 gene +49 AA genotype and +49 A allele was significantly higher in pancreatic patients compared to controls (odds ratio [OR]=2.20, 95% confidence interval [CI]: 1.23-2.95, p=0.007; OR=1.32, 95% CI: 1.03-1.69, p=0.029; and OR=1.47, 95% CI: 1.03-2.09, p=0.033). These results indicate that the CTLA-4 +49G/A polymorphism is associated with increased risk of pancreatic cancer.     

CTLA-4 polymorphisms and systemic lupus erythematosus (SLE): a meta-analysis

Several reports demonstrate association between variants of the cytotoxic T lymphocyte antigen-4 (CTLA-4) and autoimmune diseases. CTLA-4 may generate autoimmunity by immune dysregulation, making CTLA-4 an attractive candidate gene for systemic lupus erythematosus (SLE) susceptibility. Previous CTLA-4 association studies with SLE, however, have produced inconsistent results. We have performed a meta-analysis to better assess the purported associations. A total of 14 independent studies (to July 2004) testing association between one or more CTLA-4 polymorphisms and SLE were used in this analysis. We have compared allele and genotype frequencies at four polymorphic sites found in exon-1 (at +49), the promoter region (at –318 and –1722), and the 3 untranslated region (3UTR) (dinucleotide repeat). We have evaluated both fixed and random effect models, depending on the presence of between-study heterogeneity. The data demonstrate that the exon-1 +49 polymorphism is significantly associated with SLE susceptibility. The overall risk, measured by odds ratio (OR), for exon-1 +49 GG genotype is 1.287 [95% confidence interval (CI)=1.031–1.562, P=0.011]. Stratification by ethnicity indicates the exon–1 +49 GG genotype is associated with SLE, at least in Asians (OR=1.293, 95% CI=1.031–1.620, P=0.026). European-derived populations have an effect of similar magnitude (OR=1.268, 95% CI=0.860–1.870, P=0.230), though not significant. Similar trends are found in allele-specific risk estimates and disease association. The OR for the exon-1 +49 risk allele (G) in Asians is 1.246 (95% CI=1.057–1.469, P=0.009), while Europeans have no evidence of allelic association (OR=0.978, 95% CI=0.833–1.148, P=0.780). In conclusion, this meta-analysis supports the CTLA-4 exon-1 +49 (A/G) polymorphism influencing the risk for developing SLE, especially in Asians.     

Association Study of Single Nucleotide Polymorphisms in XRCC1 Gene with the Risk of Gastric Cancer in Chinese Population

Gastric cancer is one of highly cancer-related deaths in the world. Previous evidence suggests that the X-ray repair cross-complementing group 1 gene (XRCC1) is one of the most important candidate genes for influencing gastric cancer risk. The objective of this study was to detect the potential association of genetic variants in XRCC1 gene with gastric cancer risk in Chinese Han population. In total, we enrolled 395 gastric cancer patients and 398 cancer-free controls in this study. The genotyping of c.910A>G and c.1804C>A genetic variants in XRCC1 gene were investigate by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and created restriction site-PCR (CRS-PCR) methods, respectively. We found the genotypes/alleles from these two genetic variants were statistically associated with the increased risk of gastric cancer (for c.910A>G, GG versus (vs.) AA: OR = 2.00, 95% CI 1.21-3.31; AG vs. AA: OR = 1.50, 95% CI 1.12-2.02; GG/AG vs. AA: OR = 1.59, 95% CI 1.20-2.10; GG vs. AG/AA: OR = 1.68, 95% CI 1.03-2.73; G vs. A: OR = 1.47, 95% CI 1.18-1.83; for c.1804C>A, AA vs. CC: OR = 2.68, 95% CI 1.46-4.94; AA vs. CA/CC: OR = 2.62, 95% CI 1.44-4.76; A vs. C: OR = 1.33, 95% CI 1.06-1.66). The allele-G of c.910A>G and allele-A of c.1804C>A genetic variants may contribute to gastric cancer susceptibility. These preliminary results indicate that these XRCC1 genetic variants are potentially related to gastric cancer susceptibility in Chinese Han population, and might be used as molecular markers.     

Cytotoxic T-lymphocyte associated antigen 4 polymorphisms and asthma risk: a meta-analysis

Background

A number of studies assessed the association of cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) gene polymorphisms with asthma in different populations. However, the results were contradictory. We performed a meta-analysis to examine the association between CTLA-4 polymorphisms and asthma susceptibility.

Methods

Pubmed, EMBASE, HuGE Navigator, and Wanfang Database were searched. Data were extracted independently by two reviewers. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations.

Results

Seventeen studies involving 6378 cases and 8674 controls were included. Significant association between +49 A/G polymorphism and asthma was observed for AA vs. AG+GG (OR = 1.18, 95% CI 1.01–1.37, P = 0.04). There were no significant associations between −318 C/T, −1147 C/T, CT60 A/G, −1722 C/T, or rs926169 polymorphisms and asthma risk.

Conclusions

This meta-analysis suggested that the +49 A/G polymorphism in CTLA-4 was a risk factor for asthma.     

Investigation of IGF1, IGF2BP2, and IGFBP3 variants with lymph node status and esophagogastric junction adenocarcinoma risk

Esophagogastric junction adenocarcinoma (EGJA) may be associated with obesity and overweight. Thus, any variant in energy metabolism–related gene may influence the development of EGJA. In this study, we recruited 720 EGJA cases and 1541 noncancer controls. We selected IGF2BP2 rs4402960 G > T, rs1470579 A > C, IGF1 rs5742612 A > G and IGFBP3 rs3110697 G > A, rs2270628 C > T and rs6953668 G > A loci and assessed the relationship of these polymorphisms with lymph node status and susceptibility of EGJA. We found that IGF2BP2 rs1470579 A > C and IGFBP3 rs6953668 G > A polymorphisms were associated with the decreased risk of EGJA ( IGF2BP2 rs1470579: CC vs AA: adjusted odds ratio [OR] = 0.65, 95% confidence interval [CI] = 0.43-0.98, P = 0.041 and CC vs AA/AC: adjusted OR = 0.62, 95% CI = 0.41-0.93, P = 0.021 and IGFBP3 rs6953668: GA vs GG: adjusted OR = 0.66, 95% CI = 0.47-0.93, P = 0.019 and GA/AA vs GG: adjusted OR = 0.68, 95% CI = 0.48-0.95, P = 0.026). However, we also found that IGF1 rs5742612 A > G polymorphism increased the risk of LNM among patients with EGJA (GG vs AA: adjusted OR = 1.88, 95% CI = 1.02-3.46, P = 0.042 and GG vs AA/AG: adjusted OR = 1.92, 95% CI = 1.06-3.47, P = 0.032). This study suggests that IGF2BP2 rs1470579 A > C and IGFBP3 rs6953668 G > A polymorphisms may decrease genetic susceptibility to EGJA in eastern Chinese Han population. In addition, our findings also indicate that IGF1 rs5742612 A > G polymorphism may increase the susceptibility of LNM among patients with EGJA.     

Association between CASP3 polymorphisms and overall cancer risk: A meta-analysis of case-control studies

Several studies inspected the relationship between caspase-3 (CASP3) polymorphisms and the risk of several human cancers, but the findings remain controversial. We conducted a meta-analysis aiming to inspect the association between CASP3 rs1049216 T>C, rs12108497 C>T, rs4647603 G>A, rs4647602 C>A, rs6948 T>G, rs2705897 A>C, and rs113420705 G>A polymorphisms and cancer risk. Eligible studies were recognized by searching the Web of Science, PubMed, Scopus, and Google Scholar databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to quantitatively evaluate the association between each polymorphism of CASP3 and cancer risk. The rs4647603 variant significantly increased the risk of cancer in an overdominant (OR, 1.44; 95% CI, 1.03-2.01; P = 0.03; AG vs AA+GG) inheritance model. Regarding the rs4647602 variant, the findings revealed that this variant was associated with protection against cancer in homozygous codominant (OR, 0.67; 95% CI, 0.56-0.80; P < 0.00001; AA vs CC), dominant (OR, 0.84; 95% CI, 0.73-0.96; P = 0.009; AC+AA vs CC), recessive (OR, 0.70; 95% CI, 0.61-0.79; P < 0.00001; AA vs AC+CC), and allele (OR, 0.81; 95% CI, 0.75-0.88; P = 0.00001; A vs C) models. The findings suggested that the rs2705897 variant significantly decreased the risk of cancer in heterozygous codominant (OR, 0.80; 95% CI, 0.67-0.94; P = 0.009; AC vs AA), dominant (OR, 0.81; 95% CI, 0.69-0.95; P = 0.009; AC+CC vs AA), overdominant (OR, 0.80; 95% CI, 0.68-0.95; P = 0.01; AC vs CC+AA), and allele (OR, 0.85; 95% CI, 0.74-0.97; P = 0.02; C vs A) models. The results did not support an association between CASP3 rs1049216 and rs6948 polymorphisms and cancer risk. In summary, the findings of this meta-analysis support an association between CASP3 polymorphisms and cancer risk. Larger and well-designed studies are desired to evaluate these associations in detail.     

Association of excision repair cross-complimentary group 1 gene polymorphisms with breast and ovarian cancer susceptibility

The role of excision repair cross-complimentary group 1 (ERCC1) gene polymorphisms in breast and ovarian cancer development has long been controversial and existing data were inconsistent. Here, we conducted a comprehensive meta-analysis to better clarify the association. Case-control studies published from December 2008 to November 2018 were assessed. The statistical analyses of the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated. Fifteen articles with 24 case-control studies and 3 ERCC1 polymorphisms were enrolled. A total of 20 923 participants including 9896 cases and 11 027 controls were analyzed. The results showed that C to T variation in the ERCC1 rs11615 (C/T) polymorphisms was correlated with breast cancer susceptibility (T vs C: OR = 1.19, 95% CI = 1.02-1.38; TT + CT vs CC: OR = 1.24, 95% CI = 1.12-1.36). ERCC1 rs3212986 (C/A) polymorphisms posed an increased risk for breast and ovarian cancer as whole (A vs C: OR = 1.12, 95% CI = 1.01-1.25; AA + CA vs CC: OR = 1.11, 95% CI = 1.02-1.22), and presented especially higher risk for ovarian cancer (A vs C: OR = 1.31, 95% CI = 1.05-1.63; AA vs CA + CC: OR = 1.66, 95% CI = 1.12-2.47; AA vs CC: OR = 1.72, 95% CI = 1.12-2.64). Meanwhile, neither overall group analyses nor stratified analyses displayed any association of ERCC1 rs2298881 (A/C) polymorphisms in breast and ovarian cancer susceptibility. This meta-analysis suggested that ERCC1 rs11615 (C/T) polymorphisms were associated with breast cancer susceptibility and rs3212986 (C/A) polymorphisms were especially correlated with ovarian cancer risk. More case-control studies with well-adjusted data and diverse populations are essential for validation of our conclusion.     

Lack of an association between -308G>A polymorphism of the TNF-α gene and liver cirrhosis risk based on a meta-analysis

TNF-α is a potential proinflammatory cytokine that plays an important role in the pathogenesis of liver cirrhosis. We investigated a possible association between TNF-α -308G>A polymorphism and liver cirrhosis risk by conducting a meta-analysis. Publications addressing the association between TNF-α -308G>A and liver cirrhosis risk were selected from the Pubmed and Embase databases. Data were extracted from the studies by two independent reviewers; odds ratio (OR) with a 95% confidence interval (CI) was calculated from these data. The meta-analysis was performed by Review Manager Version 5.0.24 and STATA Version 9.2. Eleven studies were retrieved, reporting a total of 1796 liver cirrhosis cases and 2113 healthy controls. A meta-analysis of these 11 studies identified no significant association between TNF-α -308G>A polymorphism and liver cirrhosis risk in all comparisons of G vs A allele; GG vs GA + AA; GG + GA vs AA; GG vs AA; GG vs GA (OR = 1.14, 95%CI = 0.85-1.55, P = 0.38; OR = 1.24, 95%CI = 0.87- 1.77, P = 0.24; OR = 0.90, 95%CI = 0.62-1.30, P = 0.57; OR = 1.03, 95%CI = 0.56-1.89, P = 0.92; OR = 1.30, 95%CI = 0.90-1.88, P = 0.17; respectively). In conclusion, we found no association between TNF-α -308G>A polymorphism and liver cirrhosis risk, both in Caucasian and Asian populations.     

Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms in cancer: a meta-analysis

Toll-like receptor 4 (TLR4) is critical in the recognition of Gram-negative bacteria serving as a key immune system effector. Recently, a number of case-control studies were conducted to investigate the association between TLR4 gene polymorphism and cancer risk, especially Asp299Gly and Thr399Ile polymorphisms. However, published data were still conflicting. In this paper, we summarized 9463 cancer cases and 10,825 controls from 22 studies and attempted to assess the susceptibility of TLR4 gene polymorphism to cancers by a synthetical meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the relationship. Our results suggested that Asp299Gly represented a risk factor on cancers in digestive system (G allele versus A allele, OR=1.64, 95% CI: 1.02-2.64; GA+GG versus AA, OR=1.64, 95% CI: 1.00-2.71) but tend to have a protective effect on prostate cancer (GG versus AA, OR=0.37, 95% CI: 0.14-0.98; GG versus GA+AA, OR=0.37, 95% CI: 0.14-0.98). Thr399Ile polymorphism was significantly associated with an elevated cancer risk in overall analysis (T allele versus C allele, OR=1.72, 95% CI: 1.27-2.33; TC versus CC, OR=1.63, 95% CI: 1.18-2.26; TT+TC versus CC, OR=1.70, 95% CI: 1.24-2.34) and especially in gastrointestinal subgroup (T allele versus C allele, OR=2.01, 95% CI: 1.40-2.89; TC versus CC, OR=1.86, 95% CI: 1.26-2.74; TT+TC versus CC, OR=1.97, 95% CI: 1.35-2.88). Further prospective researches with larger numbers of worldwide participants are warranted to draw comprehensive and true conclusions.     

Common polymorphisms (rs2241766 and rs1501299) in the ADIPOQ gene are not associated with hypertension susceptibility among the Chinese

The ADIPOQ gene has been implicated in the etiology of hypertension. However, the results have been inconsistent. In this study, a meta-analysis was performed to assess the associations of ADIPOQ polymorphisms with hypertension risk among the Chinese. Published literature from PubMed, CNKI and Wanfang Data were retrieved. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed- or random-effects model. Six studies (1,812 cases and 2,631 controls) for rs2241766 polymorphism and four studies (1,449 cases and 2,175 controls) for rs1501299 polymorphism were identified. A marginally significant association was observed for rs2241766 polymorphism under recessive genetic model (GG vs. GT+TT: OR = 1.22, 95 % CI 1.01-1.48) and for rs1501299 polymorphism under heterogeneous co-dominant model (TG vs. GG: OR = 0.86, 95 % CI 0.75-0.99) and dominant model (TT+TG vs. GG: OR = 0.85, 95 % CI 0.74-0.98). In addition, under other genetic models, there was no significant association for rs2241766 polymorphism (GG vs. TT: OR = 1.20, 95 % CI 0.98-1.48; GT vs. TT: OR = 0.97, 95 % CI 0.85-1.10; GG+GT vs. TT: OR = 1.01, 95 % CI 0.90-1.15) and for rs1501299 polymorphism (TT vs. GG: OR = 0.82, 95 % CI 0.62-1.08; TT vs. TG+GG: OR = 0.87, 95 % CI 0.66-1.14). However, the associations above were not robust by sensitivity analysis. The present meta-analysis indicated the limited evidence of the significant associations between ADIPOQ gene polymorphisms and hypertension susceptibility among the Chinese.     

Relationship between Interleukin-10 ?1082A/G Polymorphism and Risk of Ischemic Stroke: A Meta-Analysis

Objective

To analyze the association between −1082A/G polymorphism in interleukin-10 (IL-10) gene and ischemic stroke (IS) risk by meta-analysis.

Methods

We 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.

Results

7 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).

Conclusion

This 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.     

Three genetic polymorphisms of homocysteine-metabolizing enzymes and risk of coronary heart disease: a meta-analysis based on 23 case-control studies

Many epidemiological studies have explored the relationships between three genetic polymorphisms of genes encoding homocysteine-metabolizing enzymes (methionine synthase [MTR] A2756G, methionine synthase reductase [MTRR] A66G, and N(5),N(10)-methylenetetrahydrofolate reductase [MTHFR] A1298C) and risk of coronary heart disease (CHD), but no conclusive results were obtained. Therefore, we performed a meta-analysis of 23 case-control studies. Odds ratio (OR) and 95% confidence interval (95% CI) were used to examine the strength of the associations. Among those primary studies, 22 studies were for Europeans, and one study focused on the MTR A2756G polymorphism in Asians. The results of combined analyses of the MTR A2756G polymorphism suggested that the G allele was associated with increased risk of CHD and myocardial infarction (MI) especially for Europeans (GG vs. AA for CHD: OR [95% CI]=1.63 [1.18-2.25], p(z)(-test)=0.001, p(heterogeneity)=0.274; GG+AG vs. AA for MI: OR [95% CI]=1.44 [1.08-1.93], p(z)(-test)=0.014, p(heterogeneity)=0.611). In addition, the G allele was also associated with higher risk CHD based on population-based case-control studies (PCC) (GG vs. AA: OR [95% CI]=1.75 [1.24-2.49], p(z)(-test)=0.002, p(heterogeneity)=0.316). The results suggested that the MTRR A66G polymorphism was not associated with risk of CHD for Europeans (AA vs. GG: OR [95% CI]=1.07 [0.59-1.94], p(z)(-test)=0.831, p(heterogeneity)<0.01). The results suggested that the C allele of the MTHFR A1298C polymorphism might be associated with the increased risk of MI for Europeans (CC vs. CA+AA: OR [95% CI]=1.37 [1.03-1.84], p(z)(-test)=0.033, p(heterogeneity)=0.668). However, when subgroup analyses for sources of controls were performed, conflicting results were obtained. The results suggested that the C allele was associated with decreased risk of CHD based on hospital-based case-control studies, but associated with increased risk of CHD based on PCC. This meta-analysis suggests that MTR A2756G polymorphism, but not MTRR A66G and MTHFR A1298C, is associated with risk of CHD for Europeans. Because of limitations and potential bias, more well-designed studies with larger sample size, especially focused on Asians and Africans, should be performed in the future.     

IL-10 Gene Polymorphisms and Susceptibility to Systemic Lupus Erythematosus: A Meta-Analysis

Background

A number of observational studies have been conducted to investigate the association of the IL-10 gene polymorphisms with systemic lupus erythematosus (SLE) susceptibility. However, their results are conflicting.

Method

We searched published case-control studies on the IL-10 polymorphisms and SLE in PubMed, EMBASE and Chinese Biomedical Literature Database. A meta-analysis was conducted using a fixed-effect or random-effect model based on between-study heterogeneity.

Results

A total of 42 studies with 7948 cases and 11866 controls were included in this meta-analysis. Among Caucasians, the CA27 allele of the IL10.G microsatellites (OR 2.38, 95% CI 1.01–5.62), the G allele of the IL-10 -1082G/A polymorphism (G vs. A: OR 1.21, 95% CI 1.02–1.44; GG vs. AA: OR 1.45, 95% CI 1.16–1.82; GG+GA vs. AA: OR 1.16, 95% CI 1.03–1.29) and its associated haplotype -1082G/−819C/−592C (OR 1.25, 95% CI 1.10–1.42) were associated with increased SLE susceptibility without or with unimportant between-study heterogeneity. Removing studies deviating from Hardy-Weinberg equilibrium (HWE) hardly changed these results. Among Asians, the CA21 allele of the IL-10.G microsatellites (OR 1.28, 95% CI 1.02–1.60) and the -1082G/−819C/−592C haplotype (OR 1.24, 95% CI 1.00–1.53) were associated with increased SLE susceptibility, but with substantial between-study heterogeneity or sensitive to HWE status. Removing studies deviating from HWE also produced statistically significant associations of the IL-10 -1082G/A (GG vs. AA: OR 3.21, 95% CI 1.24–8.28; GG vs. AA+GA: OR 2.85, 95% CI 1.19–6.79) and -592C/A polymorphisms (CC+CA vs. AA: OR 0.69, 95% CI 0.51–0.94) with SLE among Asians.

Conclusion

This meta-analysis showed that the IL10.G microsatellites, the IL-10 -1082G/A and -592C/A polymorphisms and the haplotype -1082G/−819C/−592C are associated with SLE susceptibility. Besides, this is the first time to report an association between the CA27 allele of the IL-10.G microsatellites and SLE among Caucasians. Further studies are needed to confirm these findings.