A meta-analysis of the association of glutathione S-transferase P1 gene polymorphism with the susceptibility of breast cancer

Glutathione S-transferase P1 (GSTP1) is one of the important mutant sites for the cancer risk at present. The conclusions of the published reports on the relationship between GSTP1 A/G gene polymorphism and the risk of breast cancer are still debated. This meta-analysis was performed to evaluate the association between GSTP1 and the risk of breast cancer. The association reports were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. 35 investigations were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and breast cancer susceptibility, consisting of 40,347 subjects (18,665 patients with breast cancer and 21,682 controls). The association between GSTP1 A/G gene polymorphism and breast cancer risk was not found for overall population, Caucasians and Africans. Interestingly, the GSTP1 A/G gene polymorphism was associated with the susceptibility of breast cancer in Asians (G allele: OR = 1.10, 95 % CI: 1.04–1.17, P = 0.001; GG genotype: OR = 1.36, 95 % CI: 1.14–1.62, P = 0.0008; AA genotype: OR = 0.92, 95 % CI: 0.85–0.98, P = 0.02). Furthermore, the GSTP1 A/G gene polymorphism was associated with the susceptibility of breast cancer for the analysis of the controls from hospital. In conclusion, GSTP1 A/G gene polymorphism is associated with the breast cancer susceptibility in Asians. However, more studies on the relationship between GSTP1 A/G gene polymorphism and the risk of breast cancer should be performed in further.     

The association between C-159T polymorphism in CD14 gene and susceptibility to tuberculosis: a meta-analysis

The association between CD14 gene C-159T polymorphism and tuberculosis (TB) susceptibility remains inconclusive. To derive a more precise estimation of the correlation, we performed a meta-analysis summarize the possible at a systematic manner. PubMed, HighWire and ScienceDirect databases covering all papers (up to November 2012) were searched. Statistical analyses were conducted by Rev-Man and STATA. Random- and fixed-effect models were used to estimate pooled odds ratios (ORs) and 95 % confidence intervals (CIs), based on between-study heterogeneity. Eight published case–control studies investigating the relationship between C-159T polymorphism in CD14 gene and TB susceptibility were included. Results showed that individuals with T allele have an increased risk of TB compared with those with C allele (OR (95 % CI) was 1.52 (1.11, 2.08) for TT vs. TC + CC, P < 0.001; 1.27 (1.01, 1.61) for T vs. C, P = 0.04). When stratified by ethnicity, variant TT homozygote carriers had an 86 % increased risk of TB in Asians (OR (95 % CI) was 1.86 (1.57, 2.20) for TT vs. TC + CC, P < 0.001), but not in Caucasians (OR (95 % CI) was TT vs. TC + CC: OR = 0.78, 95 % CI = 0.51–1.21, P = 0.61). This meta-analysis suggests that C-159T polymorphism in CD14 gene is associated with increased risk of TB, especially in Asians, but not in Caucasians.     

MDR1 C3435T polymorphism and inflammatory bowel disease risk: a meta-analysis

The C3435T polymorphism of the multidrug resistance gene (MDR1) has been implicated in inflammatory bowel disease (IBD) risk, but the reported results are inconsistent. Here we performed a meta-analysis to evaluate the association between C3435T polymorphism and the risk of IBD using all case–control studies published before February 2013 according to PubMed and Web of Science. A total of 13 case–control studies, including 6,757 cases and 4,295 controls, were included. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed- or random-effects model. Overall, no evidence has indicated that the C3435T polymorphism was associated with the susceptibility to IBD (dominant model: OR = 1.05, 95 % CI: 0.96–1.16; CT vs. CC: OR = 1.06, 95 % CI: 0.95–1.17; TT vs. CC: OR = 1.04, 95 % CI: 0.92–1.17; recessive model: OR = 0.99, 95 % CI: 0.90–1.09). Besides, stratified analysis by clinical type also indicated that no significant association between MDR1 C3435T and the risk of Crohn’s disease and ulcerative colitis was observed. This meta-analysis indicated that the C3435T polymorphism of MDR1 may not confer susceptibility to IBD.     

Quantitative assessment of the associations between MTHFR C677T and A1298C polymorphisms and risk of fractures: a meta-analysis

Many studies have investigated the associations between methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and risk of fractures, but the impact of MTHFR polymorphisms on fractures risk is unclear owing to the obvious inconsistence among those studies. This study aims to quantify the strength of association between MTHFR C677T and A1298C polymorphisms and risk of fractures. We searched the PubMed, Embase and Wanfang databases for articles relating the association between MTHFR C677T and A1298C polymorphisms and risk of fractures in humans. We estimated summary odds ratios (ORs) with their confidence intervals (CIs) to assess the associations. Meta-analyses suggested MTHFR C677T polymorphism was associated with increased risk of any site fractures (for T vs. C, OR = 1.17, 95 % CI 1.03–1.32; for TT vs. CC, OR = 1. 31, 95 % CI 1.11–1.54; for TT vs. CT, OR = 1.22, 95 % CI 1.04–1.43; for TT vs. CT/CC, OR = 1.31, 95 % CI 1.13–1.51). Besides, MTHFR A1298C polymorphism was also associated with increased risk of any site fractures. Subgroup meta-analyses suggested MTHFR C677T polymorphism was associated with increased risk of vertebral fractures under three genetic contrast modes (for TT vs. CC, OR = 1.43, 95 % CI 1.05–1.95; for TT vs. CT, OR = 1.36, 95 % CI 1.01–1.85; for TT vs. CT/CC, OR = 1.50, 95 % CI 1.17–1.91), but there was no association between MTHFR C677T polymorphism and risk of hip fractures and non-vertebral fractures (all P values were more than 0.05). Thus, individuals with homozygote genotype TT of MTHFR C677T have obviously increased risk of vertebral fractures compared those with heterozygote genotype CT or homozygote genotype CC. There is no association between MTHFR C677T polymorphism and risk of hip fractures and non-vertebral fractures.     

GPX1 gene Pro200Leu polymorphism, erythrocyte GPX activity, and cancer risk

A meta-analysis was conducted to assess the effect of glutathione peroxidase1 (GPX1) gene Pro200Leu (rs1050450) polymorphism on cancer risk. A comprehensive search was performed to identify all studies on the association of GPX1 gene Pro200Leu polymorphism with cancer risk. The fixed or random effect pooled measure was selected based on homogeneity test among studies. Heterogeneity among studies was evaluated using the I ². Potential sources of between-study heterogeneity were explored by meta-regression and the sensitivity analysis. Publication bias was estimated using Egger’s linear regression test. 35 published articles with 36 results were identified involving 16,920 cases and 19,946 controls. Results from the articles that both obeyed Hardy–Weinberg equilibrium in controls and met high quality design, showed no significant association of GPX1 gene Pro200Leu polymorphism with cancer risk in any of dominant (OR = 1.05, 95 %CI = 0.98–1.12), recessive (OR = 1.04 (0.95–1.13), and TT versus CC (OR = 1.05, 95 %CI = 0.97–1.15) models, and the findings were consistent considering the stratified analysis by cancer type. However, multivariate-adjusted ORs from articles that both obeyed Hardy–Weinberg equilibrium in controls and met high quality design, showed a significant association considering dominant (OR = 1.22, 95 %CI = 1.06–1.41), TT versus CC (OR = 1.16, 95 %CI = 1.02–1.32) models, and a marginally significant association was found considering TC versus CC (OR = 1.11, 95 %CI = 0.99–1.25) model. And compared with the CC genotype, the erythrocyte GPX activity was significantly lower for TT genotype: the standardized mean difference (SMD) = ?0.37, 95 %CI = (?0.624, ?0.118), and CT genotype: SMD = ?0.19, 95 %CI = (?0.37, ?0.002). The association of GPX1 gene Pro200Leu polymorphism with cancer risk might be influenced by confounders.     

Association of CDKN1B gene polymorphisms with susceptibility to breast cancer: a meta-analysis

A number of case–control studies have been conducted to investigate the association of CDKN1B gene polymorphisms with breast cancer. However, these studies reported conflicting results. The aim of our study was to quantitatively summarize the association of CDKN1B gene polymorphisms with breast cancer. Systemic searches of the PubMed, Excerpta Medica Database, and Chinese Biomedical Literature Database databases were performed, with the last report up to Oct 2012. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of the association. Seven studies including 6,822 cases and 7,186 controls were involved in this meta-analysis, which was performed for two CDKN1B gene polymorphisms (rs2066827 and rs34330). Significant association was found for rs34330 polymorphism (T versus C: OR = 1.10, 95 % CI = 1.03–1.18, P = 0.003; CT + TT versus CC: OR = 1.38, 95 % CI = 0.98–1.93, P = 0.07; TT versus CC + CT: OR = 1.06, 95 % CI = 0.93–1.21, P = 0.38; TT versus CC: OR = 1.23, 95 % CI = 1.04–1.45, P = 0.02; CT versus CC: OR = 1.42, 95 % CI = 0.97–2.09, P = 0.07), but not for rs2066827 polymorphism (G versus T: OR = 0.99, 95 % CI = 0.91–1.08, P = 0.84; TG + GG versus TT: OR = 0.98, 95 % CI = 0.89–1.08, P = 0.69; GG versus TT + TG: OR = 1.04, 95 % CI = 0.83–1.30, P = 0.75; GG versus TT: OR = 1.03, 95 % CI = 0.82–1.30, P = 0.77; TG versus TT: OR = 0.97, 95 % CI = 0.88–1.08, P = 0.58). This meta-analysis suggests that breast cancer may be associated with CDKN1B gene rs34330 polymorphism, but not rs2066827 polymorphism.     

A meta-analysis of the relationship between glutathione S-transferase T1 null/presence gene polymorphism and the risk of lung cancer including 31802 subjects

The relationship between glutathione S-transferase T1 (GSTT1) null/presence gene polymorphism and the risk of lung cancer from the published reports are still conflicting. This study was conducted to evaluate the relationship between GSTT1 null/presence gene polymorphism and the risk of lung cancer using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on July 1, 2012, and eligible investigations were included and synthesized using meta-analysis method. 51 reports were recruited into this meta-analysis for the association of null genotype of GSTT1 with lung cancer susceptibility, consisting of 15,140 patients with lung cancer and 16,662 controls. There was a marked association between GSTT1 null genotype and lung cancer risk in overall populations (OR = 1.15, 95 % CI 1.04–1.27, P = 0.007). Furthermore, GSTT1 null genotype was associated with the lung cancer risk in Asians (OR = 1.47, 95 % CI 1.23–1.76, P < 0.0001). However, GSTT1 null genotype was not associated with the risk of lung cancer in Caucasians, Brazilian population and Africans. In conclusion, GSTT1 null genotype is associated with the lung cancer in overall populations and in Asians.     

The association between common genetic variant of microRNA-499 and cancer susceptibility: a meta-analysis

Published data on the association between microRNA-499 (miR-499) rs3746444 T>C polymorphism and cancer susceptibility are inconclusive. To derive a more precise estimation of this relationship, a comprehensive meta-analysis was performed on nine published studies, with a total sample of 4,794 cases and 5,971 controls. Overall, no significant association was found between miR-499 polymorphism and cancer risk after all studies were pooled into the meta-analysis. However, in the subgroup analysis by ethnicity, significant association with an increased risk was found in Asian (CC vs. TT: OR = 1.439, 95 % CI = 1.118–1.852, P = 0.005, p-heterogeneity = 0.116). Moreover, in the the subgroup analysis by cancer type, this SNP was associated with an increased risk of breast cancer in the recessive model (OR = 1.077, 95 % CI = 1.008–1.151, P = 0.028, p-heterogeneity = 0.125). Our findings support the view that miR-499 rs3746444 T>C polymorphism is associated with breast cancer and the C allele can increase cancer susceptibility in Asian.     

Meta-analysis demonstrates lack of association of the GSK3B −50C/T polymorphism with risk of bipolar disorder

Published data on the association between GSK3B ?50C/T (rs334558) and bipolar disorder (BD) are inconclusive. We performed this meta-analysis to evaluate the relationship of this single-nucleotide polymorphism with the susceptibility, and with the age at onset of BD. A literature search was conducted though PubMed, EMBASE, Web of Science and China National Knowledge Infrastructure databases to identify relevant studies up to February 14, 2014. We identified a total of 6 publications including 1,251 cases and 1,804 controls to investigate the effect of GSK3B ?50C/T on BD risk, and found no significant association in any genetic models (C vs. T: OR = 1.03, 95 % CI: 0.92–1.15; CC vs. TT+TC: OR = 1.04, 95 % CI: 0.84–1.28; TC+CC vs. TT: OR = 1.16, 95 % CI: 0.97–1.39; and CC vs. TC vs. TT: OR = 1.08, 95 % CI: 0.96–1.22). Subgroup analysis by ethnicity did not change the results. The association between GSK3B ?50C/T and age at onset of BD was explored by 6 identified studies with a total of 659 BD type I patients. Similarly, we did not observe significant results in any genetic models (TC+CC vs. TT: SMD = 0.20, 95 % CI: ?0.07 to 0.47; CC vs. TT+TC: SMD = 0.11, 95 % CI: ?0.10 to 0.32; CC vs. TT: SMD = 0.32, 95 % CI: ?0.13 to 0.77). The power analysis and tests for publication bias ensured the reliability of our results. In summary, this meta-analysis suggests that the functional polymorphism ?50C/T within the GSK3B gene promoter is unlikely to relate with BD risk. However, more larger and well-designed studies are still needed to yield a conclusive result on the topic.     

Association of TGF-β1 +869C/T promoter polymorphism with susceptibility to autoimmune diseases: a meta-analysis

Many case–control studies have investigated the role of TGF-β1 gene +869C/T promoter polymorphism in autoimmune diseases, but the results are inconsistent. To clarify this point, we performed a meta-analysis based on all available studies in Pubmed, Elsevier Science Direct, Google Searching, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure. Crude odds ratios (ORs) with 95 % confidence intervals were calculated to estimate the strength of the association. A fixed or random effects model was used on the basis of heterogeneity. A total of 21 papers including 2,693 cases and 3,036 controls were considered in the current meta-analysis. These studies encompass two ankylosing spondylitis (AS), eight rheumatoid arthritis (RA), four systemic lupus erythematosus (SLE), and seven systemic sclerosis (SSc). The results showed that TGF-β1 +869C/T promoter polymorphism were associated with susceptibility to RA (CC vs. TT: OR = 0.65, 95 % CI = 0.48–0.88, P = 0.005; CC vs. CT + TT: OR = 0.56, 95 % CI = 0.45–0.69, P = 0.000; C vs. T: OR = 0.81, 95 % CI = 0.71–0.93, P = 0.003). When stratified by race, significant association was observed only in Asian population. However, we failed to reveal the association between this gene promoter polymorphism and AS, SLE, and SSc. Therefore, this meta-analysis suggests a possible association between TGF-β1 +869C/T promoter polymorphism and RA, especially in Asian population.     

Associations between FCGR2A rs1801274, FCGR3A rs396991, FCGR3B NA1/NA2 polymorphisms and periodontitis: a meta-analysis

The aim of this study was to determine whether the Fcγ receptors (FCGRs) polymorphisms confer susceptibility to periodontitis in ethnically different populations. We did a literature search using PubMed and Embase, and conducted a meta-analysis on the associations between the FCGR2A H131R (rs1801274), FCGR3A F158V (rs396991), and FCGR3B NA1/NA2 polymorphisms and periodontitis using allele contrast, the recessive model, the dominant model, and the homozygote contrast. A total of 17 separate comparisons with 1,421 patients with periodontitis and 1,454 controls, involving six Caucasian, six East Asian, two African and one South Asian population were considered in the meta-analysis. Meta-analysis of the FCGR2A H131R polymorphism showed no association between periodontitis and the FCGR2A R allele (OR = 0.987, 95 % CI = 0.881–1.107, p = 0.827). Stratification by ethnicity revealed an association between the RR+RH genotype with periodontitis in Caucasian population (OR = 0.624, 95 % CI = 0.479–0.813, p = 4.7 × 10^?5), but not in East Asian, and African populations. Meta-analysis of the FCGR3A F158V polymorphism revealed an association between the FCGR3A V allele and periodontitis is in Caucasians (OR = 1.457, 95 % CI = 1.014–2.092, p = 0.042), but not in East Asians and Africans. In addition, analysis using the dominant model and homozygote contrast showed the same pattern for the FCGR3A V allele. Meta-analysis of the FCGR3B NA1/NA2 polymorphism using the recessive model revealed a significant association between the NA2/NA2 genotype and periodontitis in aggressive periodontitis (OR = 2.853, 95 % CI = 1.673–4.863, 1.1 × 10^?5). This meta-analysis demonstrates that the FCGR2A, and FCGR3A polymorphisms may confer susceptibility to periodontitis in Caucasians, and that the FCGR3B polymorphism may be associated with susceptibility to aggressive periodontitis.     

Association of vitamin D binding protein polymorphism with long-term kidney allograft survival in Hispanic kidney transplant recipients

Polymorphism of genes encoding components of the vitamin D pathway including vitamin D receptor (VDR) and vitamin D binding protein (VDBP), have been widely explored due to the complex role played by vitamin D in renal transplant outcomes. In this study, we investigated whether polymorphisms of genes encoding VDR and VDBP were associated with allograft survival or acute rejection (AR) among a Hispanic kidney transplant population. A total of 502 Hispanic renal allograft recipients at the St. Vincent Medical Center between 2001 and 2010 were genotyped for four different single nucleotide polymorphisms of VDR: FokI C>T (rs2228570), BsmI G>A (rs1544410), ApaI T>G (rs7975232), and TaqI T>C (rs731236). We also performed genotyping for one common polymorphism in the VDBP gene (rs4588). Survival was significantly improved for patients who were homozygous GG for the rs4588 G>T allele in the VDBP gene (GG vs. GT + TT, OR = 0.63, p = 0.02) while GT genotype was associated with a higher risk of graft loss (GT vs. GG + TT, OR = 1.67, p = 0.01). We found no association for polymorphic markers in VDR with allograft survival and AR. The frequency of the haplotype GTCG (in the order of VDR FokI C>T, BsmI G>A, ApaI T>G, and TaqI T>C), was significantly different in the patients with graft rejection compared to the control (p = 0.007) while ACCA haplotype was found to be associated with graft loss (p = 0.02). Hence, the VDBP G>T polymorphism (rs4588) and two haplotypes (GTCG and ACCA) of VDR appear to be associated with renal allograft outcomes among Hispanic allograft recipients.     

Angiotensinogen T174M and M235T Variants and Hypertension in the Hani and Yi Minority Groups of China

A case–control study of 538 individuals investigated whether the angiotensinogen gene (AGT) might be implicated in the pathogenesis of essential hypertension in the Hani and Yi populations of China. Genotypes for two diallelic DNA polymorphisms observed at amino acid residues 174 (T174M) and 235 (M235T) within the coding sequence were determined. M235T and T174M genotyping with PCR-RFLP was performed in 267 normotensive subjects and 271 hypertensive subjects. No significant difference was found between normotensives and hypertensives in genotype distribution and allele frequency for either M235T or T174M in the Hani or the Yi populations (P > 0.05). Relative to carriers of the 235T/235T and 174T/174T combination, the others had a significantly elevated risk of hypertension (OR = 1.62, 95% CI 1.02–2.59; P = 0.043) in the Hani population. The AGT M235T and T174M variants in combination may play a role in the genetic predisposition to develop essential hypertension in the Hani minority of China.     

Quantitative analysis of the association between interleukin-10 1082A/G polymorphism and susceptibility to sepsis

There are some epidemiological studies investigating the association between interleukin-10 (IL-10) 1082A/G polymorphism and sepsis susceptibility reporting conflicting findings. Our work tried to further quantitatively assess the association of the IL-10 1082A/G polymorphism with sepsis susceptibility through a systematic review and meta-analysis. A total of eleven studies with 2,528 subjects were finally included into the meta-analysis. Pooled odds ratios (ORs) and corresponding 95 % confidence intervals (95 % CIs) were calculated with random-effects model or fixed-effects model based on the heterogeneity among the included studies. Meta-analysis of all 11 studies showed that there was an obvious association between IL-10 1082A/G polymorphism and sepsis susceptibility under the allele comparison model (G vs A) and the codominant model (GG vs AA) (for G vs A: OR = 0.83, 95 % CI 0.72–0.96, P = 0.011; for GG vs AA: OR = 0.67, 95 % CI 0.47–0.96, P = 0.029). Subgroup analysis by ethnicity showed that there was an obvious association between IL-10-1082A/G polymorphism and sepsis susceptibility in Asians under three comparison models (for G vs A: OR = 0.75, 95 % CI 0.62–0.91, P = 0.004; for GG vs AA: OR = 0.39, 95 % CI 0.21–0.73, P = 0.003; for GG vs AA/AG: OR = 0.36, 95 % CI 0.14–0.92, P = 0.032), but there was no similar association in Caucasians under all four comparison models. Our meta-analysis reveals that the IL-10-1082A/G polymorphism has an association with the susceptibility to sepsis in Asian populations. Further studies are needed to investigate the effect of IL-10-1082A/G polymorphism on sepsis susceptibility in Caucasians.     

A functional variant of pre-miRNA-196a2 confers risk for Behcet’s disease but not for Vogt–Koyanagi–Harada syndrome or AAU in ankylosing spondylitis

This study aimed to investigate the predisposition of common pre-miRNA SNPs with Behcet’s disease (BD), Vogt–Koyanagi–Harada (VKH) syndrome and acute anterior uveitis (AAU) associated with ankylosing spondylitis (AS). A two-stage association study was carried out in 859 BD, 400 VKH syndrome, 209 AAU⁺AS⁺ patients and 1,685 controls all belonging to a Chinese Han population. Genotyping, the expression of miR-196a and Bach1 (the target gene of miR-196a), cell proliferation, cytokine production were examined by PCR–RFLP, real-time PCR, CCK8 and ELISA. In the first stage study, the results showed significantly increased frequencies of the miR-196a2/rs11614913 TT genotype and T allele in BD patients (adjusted P _c = 0.024, OR = 1.63; adjusted P _c = 5.4 × 10^?3, OR = 1.45, respectively). However, no significant association of the tested SNPs with VKH and AAU⁺AS⁺ patients was observed. The second stage and combined studies confirmed the association of rs11614913 with BD (TT genotype: adjusted P _c = 6×10^?5, OR = 1.53; T allele: adjusted P _c = 8×10^?6, OR = 1.35; CC genotype: adjusted P _c = 0.024, OR = 0.68). A stratified analysis showed an association of the rs11614913 TT genotype and T allele with the arthritis subgroup of BD (P _c = 5.3 × 10^?3, OR = 1.89; P _c = 0.015, OR = 1.56, respectively). Functional experiments showed a decreased miR-196a expression, an increased Bach1 expression and an increased production of IL-1β and MCP-1 in TT cases compared to CC cases (P = 0.023, P = 0.0073, P = 0.012, P = 0.002, respectively). This study shows that a functional variant of miR-196a2 confers risk for BD but not for VKH syndrome or AAU⁺AS⁺ by modulating the miR-196a gene expression and by regulating pro-inflammatory IL-1β and MCP-1 production.     

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

The aim of this study was to summarize results on the association of cytotoxic T-lymphocyte antigen-4 (CTLA-4) promoter exon-1 +49 and 1722T/C polymorphism with systemic lupus erythematosus (SLE) susceptibility by using the meta-analysis. We searched all the publications about the association between CTLA-4) promoter exon-1 +49 and 1722T/C polymorphism and SLE from PubMed, Elsevier Science Direct, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wanfang (Chinese). 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 17 independent studies (to June 2012) testing association between one or more CTLA-4 polymorphisms and SLE were used in this analysis. We have compared allele and genotype frequencies at two polymorphic sites found in exon-1 (at +49) and the promoter region (at ?1722). The data demonstrate that the exon-1 +49 polymorphism is associated with SLE susceptibility in Asian population. The overall risk, measured by odds ratio (OR), stratification by ethnicity indicates the exon-1 +49 GG+GA genotype is associated with SLE, at least in Asians (OR = 0.85, 95 % CI = 0.73–0.99, P = 0.04 for GG+GA vs. AA; OR = 0.85, 95 % CI = 0.72–1.00, P = 0.05 for AG vs. AA). Similar trends are found in allele-specific risk estimates and disease association. Overall, there was significant association between the 1722T/C polymorphism and overall SLE risks (OR = 0.78, 95 % CI = 0.63–0.97, P = 0.04 for GG+GA vs. AA, OR = 0.87, 95 % CI = 0.76–0.99, P = 0.04 for G vs. A) in Asian population.In summary, this meta-analysis demonstrates that the CTLA-4 promoter +49A/G and promoter ?1722C/T polymorphism may confer susceptibility to SLE, especially in Asian-derived population.     

Significant association between GSTT1 null genotype and risk of asthma during childhood in Caucasians

Asthma is a complex multifactorial disorder and its management requires a better understanding of its various pathogenesis and mechanisms. Previous studies assessing the association between glutathione S-transferase T1 (GSTT1) null genotype and asthma risk during childhood reported conflicting results. To get a more precise estimation of the association between GSTT1 null genotype and risk of asthma during childhood, we performed a meta-analysis of 16 studies with a total of 18,558 subjects. Subgroup analyses were performed by ethnicity. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 %CI) was used to assess the association. Overall, there was a significant association between GSTT1 null genotype and increased risk of children asthma (OR = 1.25, 95 % CI, 1.02–1.54; P = 0.032). Subgroup analyses showed GSTT1 null genotype was associated with increased risk of children asthma in Caucasians (OR = 1.46, 95 % CI, 1.04–2.03; P = 0.027), but not in Asians (OR = 1.03, 95 % CI, 0.55–1.94; P = 0.928) and Africans (OR = 1.33, 95 % CI, 0.92–1.91; P = 0.127). There was no evidence of publication bias in the subgroup analysis of Caucasians. In conclusion, there is a significant association between GSTT1 null genotype and risk of asthma during childhood in Caucasians. More well-designed epidemiological studies are needed to further assess this association in Asians and Africans.     

Relationships between PON1 Q192R polymorphism and clinical outcome of antiplatelet treatment after percutaneous coronary intervention: a meta-analysis

This meta-analysis was performed to assess the relationships between the PON1 Q192R (rs662 T>C) polymorphism and the clinical outcome of antiplatelet treatment after percutaneous coronary intervention (PCI). A range of electronic databases were searched: Web of Science (1945–2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966–2013), EMBASE (1980–2013), CINAHL (1982–2013) and the Chinese Biomedical Database (CBM) (1982–2013) without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. The crude odds ratio (OR) with their 95 % confidence interval (CI) were calculated. Six clinical cohort studies with a total number of 5,189 patients undergoing PCI for coronary heart disease were included. Our meta-analysis revealed that the PON1 Q192R polymorphism was correlated with an increased risk of major adverse cardiovascular events (MACE) in patients receiving antiplatelet treatment after PCI (C allele vs. T allele: OR = 1.22, 95 % CI 1.04–1.43, P = 0.014; CT+CC vs. TT: OR = 1.38, 95 % CI 1.03–1.86, P = 0.029; CC vs. TT: OR = 1.45, 95 % CI 1.05–1.99, P = 0.024; respectively), especially among Asians. Furthermore, we found significantly positive correlations between the PON1 Q192R polymorphism and the incidence of stent thrombosis in patients receiving antiplatelet treatment after PCI (C allele vs. T allele: OR = 1.42, 95 % CI 1.08–1.87, P = 0.011; CT+CC vs. TT: OR = 1.93, 95 % CI 1.01–3.67, P = 0.046; CC vs. TT: OR = 2.18, 95 % CI 1.09–4.35, P = 0.027; respectively). Our meta-analysis of clinical cohort studies provides evidence that the PON1 Q192R polymorphism may increase the risk of MACE and stent thrombosis in patients receiving antiplatelet treatment after PCI.     

Significant association between GSTT1 null genotype and susceptibility to pancreatic cancer

Many studies have investigated the association between glutathione S-transferase T1 (GSTT1) polymorphism and risk for pancreatic cancer, but those studies have yielded contradictory findings on the association. We performed a comprehensive search in the PubMed, EMBASE, and the Chinese National Knowledge Infrastructure databases to identify relevant studies. A meta-analysis was performed to examine the association between GSTT1 polymorphism and susceptibility to pancreatic cancer by calculating the pooled odds ratios (ORs) and corresponding 95 % confidence intervals (95 % CIs). Eight studies involving a total of 4,437 individuals were included. Overall, significantly increased pancreatic cancer risk was associated with GSTT1 null genotype when all studies were pooled into the meta-analysis (random effects OR = 1.61, 95 % CI 1.06–2.44; P = 0.025). Significantly increased risk of pancreatic cancer was also found for GSTT1 null genotype in Asians when stratified by ethnicity (fixed effects OR = 2.67, 95 % CI 1.74–4.09; P < 0.001). The findings demonstrate that GSTT1 null genotype have a modest effect on the genetic susceptibility to pancreatic cancer, and GSTT1 null genotype is associated with increased risk of pancreatic cancer.