Association between the −1438G/A and T102C polymorphisms of 5-HT2A receptor gene and obstructive sleep apnea: a meta-analysis

The serotonin 2A (5-HT2A) receptor has been implicated in obstructive sleep apnea (OSA). Single nucleotide polymorphisms (SNPs) in the 5-HT2A gene have been found in OSA, the most common being ?1438G/A and T102C; however, studies of the association between 5-HT2A SNPs and OSA risk have reported inconsistent findings. A meta-analysis was performed to quantitatively review the association between ?1438G/A and T102C SNPs and OSA. Five studies, including 791 subjects for ?1438G/A genotype and 1,068 subjects for T102C genotype, were selected. Pooled data analysis of the ?1438G/A genotype indicated a significantly increased OSA risk was associated with two variant genotypes (AA vs. AG+GG: OR 3.023, 95 % CI 2.169–4.213, P = 0.506 for heterogeneity; A allele carriers vs. GG: OR 1.938, 95 % CI 0.879–4.274, P = 0.012 for heterogeneity). Stratification analysis by gender supported the association in males, but not females. For the T102C genotype, no significantly increased OSA risk was associated with the two variant genotypes (CC vs. CT+TT: OR 1.065, 95 % CI 0.787–1.442, P = 0.361 for heterogeneity; C allele carriers vs. TT: OR 0.979, 95 % CI 0.737–1.3, P = 0.9 for heterogeneity).In conclusions, meta-analysis indicated that the ?1438G/A, and not T102C, polymorphism of 5-HT2A is a positive risk factor of OSA, especially in males.     

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.     

MTHFR polymorphisms and ovarian cancer risk: a meta-analysis

The C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) have been reported to alter the risk of ovarian cancer. However, the results are still inconclusive. For better understanding of the effect of these two polymorphisms on ovarian cancer risk, a meta-analysis was performed. An extensive search was performed to identify all case–control studies investigating such association. The strength of association between these two polymorphisms and ovarian cancer risk was assessed by odds ratio (OR) with the corresponding 95?% confidence interval (95?% CI). 3,496 cases and 3,631 controls for C677T polymorphism and 3,280 cases and 3,346 controls for A1298C polymorphism were included in this meta-analysis. The results suggested that there were no significant associations between C677T and A1298C polymorphisms and ovarian cancer risk in overall comparisons in all genetic models (For C677T: TT vs. CC: OR?=?0.94, 95?% CI?=?0.71–1.24, P?=?0.65; CT vs. CC: OR?=?1.03, 95?% CI?=?0.93–1.14, P?=?0.57; TT/CT vs. CC: OR?=?1.01, 95?% CI?=?0.88–1.16, P?=?0.87; TT vs. CC/CT: OR?=?0.93, 95?% CI?=?0.72–1.20, P?=?0.58. For A1298C: CC vs. AA: OR?=?1.05, 95?% CI?=?0.88–1.25, P?=?0.65; CA vs. AA: OR?=?0.98, 95?% CI?=?0.88–1.08, P?=?0.66; CC/CA vs. AA: OR?=?0.99, 95?% CI?=?0.90–1.09, P?=?0.85; CC vs. AA/CA: OR?=?1.06, 95?% CI?=?0.90–1.26, P?=?0.46). Subgroup analysis based on ethnicities and influence analysis did not perturb the results. In conclusion, the results of this meta-analysis indicate that the MTHFR C677T and A1298C polymorphisms are not associated with ovarian cancer risk, especially in Caucasians.     

The association between MTHFR C677T polymorphism and ovarian cancer risk: a meta-analysis of 18, 628 individuals

Methylenetetrahydrofolate reductase (MTHFR) enzyme plays an important role in folate metabolism and MTHFR polymorphisms have been suggested to be associated with risk of various cancers. MTHFR C677T polymorphism is a common genetic alteration and may affect the host susceptibility to ovarian cancer. The aim of this study was to investigate the association between MTHFR C677T polymorphism and ovarian cancer risk by performing a meta-analysis. Pubmed, Embase, Web of Science and Chinese Biomedical Database (CBM) databases were searched for case–control studies investigating the association between MTHFR C677T polymorphism and ovarian cancer. Odds ratio (OR) and its 95 % confidence interval (95 % CI) was used to assess this possible association. 13 individual case–control studies from 10 publications with a total of 18, 628 subjects (5, 932 cases and 12, 696 controls) were included into this meta-analysis. Meta-analyses showed there was no association between MTHFR C677T polymorphism and ovarian cancer risk in Caucasians under all five genetic models (All P values for the pooled ORs were more than 0.05), whereas there was an obvious association between MTHFR C677T polymorphism and ovarian cancer risk in Asians under four genetic models (for T vs C, OR (95 % CI) = 1.38(1.19–1.61); for TT vs CC, OR (95 % CI) = 2.32(1.63–3.29); for TT vs TC+CC, OR (95 % CI) = 2.04(1.47–2.85); for TT+TC vs CC, OR (95 % CI) = 1.36(1.12–1.65)). Subgroup analyses suggested ethnicity was the major source of heterogeneity. This meta-analysis supports an association between MTHFR C677T polymorphism and ovarian cancer risk, and there might be a race-specific effect in this association. Further studies with large sample size and careful design are needed to identify this association more comprehensively.     

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.     

Association of VEGF gene polymorphisms with advanced retinopathy of prematurity: a meta-analysis

Published data on the association of vascular endothelial growth factor (VEGF) gene polymorphisms with retinopathy of prematurity (ROP) are inconclusive. The aim of the study was to assess the association by using meta-analysis. Data were collected from the following electronic databases: PubMed, Elsevier Science Direct, Excerpta Medica Database, Cochrane Library and China National Knowledge Infrastructure, with the last report up to 30 April, 2012. The odds ratio (OR) and its 95?% confidence interval (95?%CI) were used to assess the strength of the association. Meta-analysis was performed in a fixed/random effect model by using the software Review Manager 4.2. A total of 7 studies based on the search criteria were involved in this meta-analysis. Meta-analysis was performed for four VEGF gene polymorphisms (?634G/C, ?460T/C, ?2578C/A and 936C/T). Significant association was found for ?460T/C polymorphism (C vs T: OR?=?0.74, 95?%CI?=?0.57–0.95, P?=?0.02; TC+CC vs TT: OR?=?0.75, 95?%CI?=?0.47–1.21, P?=?0.24; CC vs TT+TC: OR?=?0.45, 95?%CI?=?0.26–0.76, P?=?0.003; CC vs TT: OR?=?0.45, 95?%CI?=?0.24–0.84, P?=?0.01; TC vs TT: OR?=?0.96, 95?%CI?=?0.59–1.57, P?=?0.87) in the VEGF gene, but not for other polymorphisms (?634G/C, ?2578C/A and 936C/T). This meta-analysis demonstrates that advanced ROP is associated with VEGF gene ?460T/C polymorphism, but not ?634G/C, ?2578C/A and 936C/T.     

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.     

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.     

Meta-analysis of vitamin D receptor gene polymorphisms and benign prostatic hyperplasia risk

The association between vitamin D receptor (VDR) gene polymorphisms and risk of benign prostatic hyperplasia (BPH) has been investigated in numerous publications, but published results remain inconclusive. Hence, we conducted this meta-analysis to derive a more precise conclusion. Four polymorphisms (Taq-I, Bsm-I, Apa-I, and Fok-I) of the VDR gene with risk of BPH from six case–control studies and one cohort study involving 2,248 individuals were identified from PubMed and China National Knowledge Internet databases up to November 20, 2013 (updated on March 5, 2014). After data extraction, the meta-analysis was performed using Comprehensive Meta-Analysis software. All four VDR polymorphisms were not associated with the risk of BPH [Taq-I: OR 0.61, 95 % CI (0.38–1.24) for tt vs. TT; Bsm-I: OR 1.27, 95 % CI (0.96–1.69) for bb vs. BB; Apa-I: OR 1.26, 95 % CI (0.64–2.46) for aa vs. AA; Fok-I: OR 0.95, 95 % CI (0.60–1.50) for ff vs. FF]. Subgroup analysis according to ethnicity for Taq-I polymorphism also showed that the polymorphism was not associated with risk of BPH for either Caucasians [OR 0.74, 95 % CI (0.31–1.78) for tt vs. TT] or Asians [OR 0.35, 95 % CI (0.11–1.11) for tt vs. TT]. However, results of this meta-analysis should be treated with caution because this meta-analysis has several limitations. We propose to conduct a high-quality study with large sample size to further identify the association between VDR gene polymorphisms and BPH susceptibility.     

Association between polymorphism of MTHFR c.677C>T and risk of cardiovascular disease in Turkish population: a meta-analysis for 2.780 cases and 3.022 controls

Cardiovascular diseases (CVDs) remain the main cause of morbidity and mortality around the world. A common polymorphism c.677C>T has been identified in the gene coding for methylenetetrahydrofolate reductase (MTHFR), which is involved in the remethylation of homocysteine, and may predispose to CVDs. A meta-analysis was performed to estimate the risk of CVDs associated with MTHFR c.677C>T in Turkish population. Published studies were retrieved from PubMed, Science Citation Index/Expanded, Google Scholar, Turkish Medline, and the Turkish Council of Higher Education Theses Database. For each study, we calculated odds ratios and 95 % confidence intervals (CI), assuming frequency of allele and homozygote comparison, dominant and recessive genetic models. Thirty-one separate studies were included and 2.780 cases/3.022 controls were involved in the current meta-analysis. Significant association was found between c.677C>T polymorphism and risk of CVD when all studies pooled with random-effects model for T versus C (OR 1.33; 95 % CI 1.11–1.59; p = 0.002), TT vs. CC (OR 1.87; 95 % CI 1.35–2.60; p = 3.53E?04), TT+CT vs. CC (OR 1.32; 95 % CI 1.06–1.64; p = 0.014) and TT vs. CT+CC (OR 1.75; 95 % CI 1.29–2.37; p = 6.57E?04). Further analysis indicated the significant association between methylenetetrahydrofolate reductase (MTHFR) TT genotype and groups with venous thrombosis, peripheral arterial thrombosis, acute MI/MI. No publication bias was observed in any comparison model. Our results of meta-analysis suggest that MTHFR c.677C>T polymorphism is associated with the CVDs in Turkish population.     

CD14 −159C/T polymorphism contributes to the susceptibility to tuberculosis: evidence from pooled 1,700 cases and 1,816 controls

CD14 is a receptor for lipopolysaccharide and plays an important role in innate immune against infections induced by microorganisms. A functional polymorphism in promoter region of CD14 gene, ?159C/T, was extensively investigated with tuberculosis (TB) risk, but the association results were inconclusive. We performed a meta-analysis to synthesize association results of CD14 ?159C/T polymorphism with TB risk from 8 studies including 1,700 TB cases and 1,816 controls. Based on the heterogeneity between studies evaluated by χ²-based Q test, a fixed- or random-effect model was applied to estimate the pooled odds ratio (OR) and 95 % confidence interval (CI). Potential publication bias was evaluated with the funnel plot as well as the linear regression asymmetry test proposed by Egger et al. We found that the ?159T allele was significantly associated with an increased risk of TB (OR 1.27, 95 % CI 1.01–1.61) as compared with ?159C allele. Individuals with ?159TT genotype showed a significantly increased risk of TB than those with ?159CT/CC genotype (OR 1.52, 95 % CI 1.11–2.08). These associations were not attributed to potential publication bias (P > 0.05 for Egger’s test). The results from this meta-analysis indicate that CD14 ?159C/T polymorphism is associated with TB predisposition and may serve as a candidate of susceptibility biomarker for TB.     

Apo A5 −1131T/C, FgB −455G/A, −148C/T, and CETP TaqIB gene polymorphisms and coronary artery disease in the Chinese population: a meta-analysis of 15,055 subjects

The Apolipoprotein A5 (APO A5) ?1131T/C, fibrinogen β (FgB) ?455G/A, ?148C/T, and cholesteryl ester transfer protein (CETP) TaqIB gene polymorphisms have been indicated to be associated with the coronary artery disease (CAD) risk, but the individual study results are still inconsistent. To explore the relationship between APO A5 ?1131T/C, FgB ?455G/A, ?148C/T, and CETP TaqIB gene polymorphisms and CAD in the Chinese population, the current meta-analysis involving 15,055 subjects from 40 individual studies was conducted. The pooled odds ratio (OR) for the association between APO A5 ?1131T/C, FgB ?455G/A, ?148C/T, and CETP TaqIB gene polymorphisms and CAD and its corresponding 95 % confidence interval (95 % CI) were evaluated by random or fixed effect model. A significant association between APO A5 ?1131T/C gene polymorphism and CAD in the Chinese population was found under an allelic (OR: 1.33, 95 % CI: 1.22–1.44, P < 0.00001), recessive (OR: 1.67, 95 % CI: 1.25–2.25, P = 0.0006), dominant (OR: 0.820, 95 % CI: 0.767–0.876, P = 1.0 × 10^?10), homozygous (OR: 2.36, 95 % CI: 1.55–3.58, P < 0.0001) and heterozygous genetic models (OR: 1.136, 95 % CI:1.075–1.200, P = 1.0 × 10^?10). A significant association between FgB ?455G/A gene polymorphism and CAD was also detected in the Chinese population under an allelic (OR: 1.50, 95 % CI: 1.25–1.81, P < 0.0001), dominant (OR: 0.864, 95 % CI: 0.819–0.912, P = 1.0 × 10^?10), homozygous (OR: 1.616, 95 % CI: 1.213–2.152, P = 0.001) and heterozygous genetic models (OR: 1.245, 95 % CI:1.138–1.361, P = 1.0 × 10^?10). No significant association was found between them under a recessive genetic model (OR: 1.124, 95 % CI: 0.844–1.497, P = 0.424). A significant association was also found between FgB ?148C/T gene polymorphism and CAD in the Chinese population under an allelic (OR: 1.34, 95 % CI: 1.06–1.71, P = 0.02), recessive (OR: 1. 65, 95 % CI: 1.02–2.69, P = 0.04), dominant (OR: 0.924, 95 % CI: 0.872–0.978, P = 0.007) and homozygous genetic models (OR: 0.968, 95 % CI: 0.942–0.995, P = 0.018). No significant association was found between them under a heterozygous genetic model (OR: 0.979, 95 % CI: 0.937–1.023, P = 0.342). In the whole Chinese population, no significant association between the CETP TaqIB gene polymorphism and CAD was found under an allelic (OR: 1.17, 95 % CI: 0.94–1.45, P = 0.15), dominant (OR: 1.46, 95 % CI: 0.80–2.67, P = 0.22) or recessive genetic models (OR: 0.68, 95 % CI: 0.32–1.44, P = 0.31). However, in the subgroup analysis stratified by ethnicity, there was a significant association between them under an allelic (OR: 1.27, 95 % CI: 1.07–1.52, P = 0.007) and dominant genetic model (OR: 2.04, 95 % CI: 1.49–2.79, P < 0.00001) in the Han subgroup. In the Chinese population, the APO A5 ?1131T/C and FgB ?455G/A, ?148C/T gene polymorphisms were implied to be associated with CAD susceptibility. The APO A5 ?1131C, FgB ?455A, and ?148T alleles might confer susceptibility to CAD. CETP TaqIB gene polymorphism was suggested to be associated with CAD susceptibility in the Chinese Han population. Carriers with B1 allele of CETP TaqIB gene might be predisposed to CAD in the Chinese Han population.     

Interleukin-10 Promoter Gene Polymorphisms and Susceptibility to Tuberculosis: A Meta-Analysis

Objective

As an update to other recent meta-analyses, the purpose of this study was to explore whether interleukin-10 (IL-10) polymorphisms and their haplotypes contribute to tuberculosis (TB) susceptibility.

Methods

We searched for published case-control studies examining IL-10 polymorphisms and TB in PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Wanfang databases and the Chinese National Knowledge Infrastructure (CNKI). Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strengths of the associations.

Results

A total of 28 studies comprising 8,242 TB patients and 9,666 controls were included in the present study. There were no significant associations between the -1082G/A, -819C/T, and -592A/C polymorphisms and TB in the pooled samples. Subgroup analyses revealed that the -819T allele was associated with an increased TB risk in Asians in all genetic models (T vs. C: OR=1.17, 95% CI=1.05-1.29, P=0.003; TT vs. CC: OR=1.37, 95% CI=1.09-1.72, P=0.006; CT+TT vs. CC: OR=1.33, 95% CI=1.09-1.63, P=0.006; TT vs. CT+CC: OR=1.17, 95% CI=1.02-1.35, P=0.03) and that the -592A/C polymorphism was significantly associated with TB in Europeans under two genetic models (A vs. C: OR=0.77, 95% CI=0.60-0.98, P=0.03; AA vs. CC: OR=0.53, 95% CI=0.30-0.95, P=0.03). Furthermore, the GCC IL-10 promoter haplotype was associated with an increased risk of TB (GCC vs. others: P=1.42, 95% CI=1.02-1.97, P=0.04). Subgroup analyses based on ethnicity revealed that the GCC haplotype was associated with a higher risk of TB in Europeans, whereas the ACC haplotype was associated with a lower TB risk in both Asians and Europeans.

Conclusions

This meta-analysis suggests that the IL-10-819T/C polymorphism is associated with the risk of TB in Asians and that the IL-10-592A/C polymorphism may be a risk factor for TB in Europeans. Furthermore, these data indicate that IL-10 promoter haplotypes play a vital role in the susceptibility to or protection against the development of TB.     

The role of endothelial nitric oxide synthase (eNOS) T‐786C,G894T,and 4a/b gene polymorphisms in the risk of idiopathic male infertility

A considerable number of infertile men have no known mechanism for their infertility. This study aims to examine if there is an association between endothelial nitric oxide synthase (eNOS) T‐786C, G894T, and 4a/b gene polymorphisms and idiopathic male infertility. Three hundred fifty‐two men with idiopathic infertility (mean age 32.4 ± 11.4 years) and 356 healthy controls (mean age 33.2 ± 11.6 years) with documented fertility were recruited in this study. Genotypes for T‐786C, G894T, and 4a/b gene polymorphisms were identified by the polymerase chain reaction–restriction fragment length polymorphism (PCR‐RFLP) analysis. The eNOS ?786CC genotype (0.310 vs. 0.081; odds ratio (OR), 3.64; 95% confidence interval (CI), 2.28–4.46; P = 0.001), 894TT genotype (0.131 vs. 0.006; OR, 3.62; 95% CI, 2.68–4.87; P = 0.001) and 4aa genotype (0.128 vs. 0.009; OR, 2.82; 95% CI, 1.88–3.89; P = 0.004) were significantly more frequent in infertile subjects. Furthermore, there was a significant difference between the group of infertile patients with azoospermia and oligoasthenoteratozoospermia (OAT) when compared by genotype distribution (?786CC vs. 786TT, 894TT vs. 894GG, and 4aa vs. 4bb) (all P < 0.01). We also found an association between the eNOS “?786C,” “894T,” and “a” alleles and an increased risk of poor semen parameters. Our data revealed a significant relationship between eNOS genotypes and the phenotype of infertility. Mol. Reprod. Dev. 77: 720–727, 2010. © 2010 Wiley‐Liss, Inc.     

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.     

Meta-analysis of association between cytokine gene polymorphisms and lung cancer risk

The aim of this study was to evaluate the association between various cytokine gene polymorphisms and lung cancer (LC) susceptibility. We searched Pubmed, Elsevier Science Direct, China National Knowledge Infrastructure database, Chinese Biomedical database, Google scholar. Totally, 20 studies involving 6,467 cases and 8,320 controls were included in the meta-analysis. The effects of eight polymorphisms, i.e. TNF-α 308G/A, IL-6 174G/C, IL-1β 31T/C, IL-1β 511C/T, COX-2 8473T/C, IL-10 1082G/A, IL-10 819C/T, and IL-10 592C/A were evaluated. The combined odds ratio (OR) with 95% confidence interval (95% CI) was calculated to estimate the strength of the association in a fixed or random effect model. Heterogeneity and publication bias were also assessed. We found a significant association between IL-10 polymorphism and LC. For IL-10 1082G/A, the overall ORs (95% CI) of the G versus A, GG versus AA, and GG/GA versus AA were 2.35 (1.16–4.76), 2.07 (1.16–3.70) and 3.17 (1.31–7.68), respectively. For IL-10 819C/T, the pooled ORs (95% CI) of the C versus T and CC versus TT were 1.27 (1.01–1.58) and 2.27 (1.32–3.89). For IL-10 592C/A, the comparison of subjects in the CC or CC/CA genotype versus AA homozygotes showed significant results (OR = 2.00, 95% CI: 1.24–3.23; OR = 1.80, 95% CI: 1.28–2.54). But, other gene polymorphisms did not reach statistical associations. IL-10 1082G/A, 819C/T and 592C/A polymorphisms might be risk factors for LC. TNF-α 308G/A, IL-6 174G/C, IL-1β 31T/C, IL-1β 511C/T, COX-2 8473T/C polymorphisms were not detected to be related to the risk for LC. Due to the limitation of the number of the studies, we should take the conclusion with caution. While, further studies are necessary for more precise association.     

XPC Lys939Gln and Ala499Val polymorphisms in colorectal cancer susceptibility: a meta-analysis of case–control studies

The XPC Lys939Gln and Ala499Val polymorphisms were likely to be involved with the development of colorectal cancer. However, there had been inconsistent reports of association. This meta-analysis of literatures was performed to draw a more precise estimation of the relationship. We systematically searched PubMed, Embase and Web of Science for relevant articles with a time limit of December 2012. The strength of association between the XPC Lys939Gln and Ala499Val polymorphisms and colorectal cancer susceptibility were assessed by odds ratio (OR) with the corresponding 95 % confidence interval (95 % CI). This meta-analysis including six case–control studies evaluated the associations between the two XPC polymorphisms (Lys939Gln, Ala499Val) and colorectal cancer susceptibility. For XPC Lys939Gln, no obvious associations were found for all genetic models [CC vs AA: OR (95 % CI) = 1.12 (0.94–1.32); CA vs AA: OR (95 % CI) = 1.08 (0.94–1.24); the dominant model: OR (95 % CI) = 1.09 (0.97–1.23); the recessive model: OR (95 % CI) = 1.07 (0.92–1.25)]. For XPC Ala499Val, no obvious associations were also not found for all genetic models [TT vs CC: OR (95 % CI) = 0.84 (0.65–1.10); CT vs CC: OR (95 % CI) = 1.00 (0.86–1.15); the dominant model: OR (95 % CI) = 0.98 (0.85–1.12); the recessive model: OR (95 % CI) = 0.87 (0.67–1.12)]. This meta-analysis suggested that both the XPC Lys939Gln and Ala499Val polymorphisms were not risk factors for increasing colorectal cancer.     

Genetic variations in CD14 promoter and acute lymphoblastic leukemia susceptibility in a Chinese population

Recent findings suggest that CD14 may play a role in tumor development. Previous case-control studies have revealed that CD14 -260C/T and -651?C/T polymorphisms contribute to the risk of human diseases. However, the relationship between these two functional polymorphisms and susceptibility to acute lymphoblastic leukemia (ALL) has not been explored. In this study, we performed a case-control study in a Chinese population. We found that an increased risk of ALL was associated with the -260?TT (odds ratio [OR]=1.85, 95% confidence interval [CI]=1.26-2.63) genotype compared with the CT or CC genotype. No significant association was found between -651?CC genotype and ALL (OR=1.13, 95% CI=0.77-1.69). Moreover, the increased risk was only associated with the -260?TT genotype in B-ALL (OR=1.99, 95% CI=1.34-3.01) but not in T-ALL (OR=1.48, 95% CI=0.79-2.84). The findings suggest that CD14-260C/T polymorphism can contribute to B-ALL risk in a Chinese population.     

MTHFR C677T polymorphism contributes to colorectal cancer susceptibility: evidence from 61 case–control studies

Methylenetetrahydrofolate reductase (MTHFR) is believed to be involved in folate metabolism which plays a critical role in carcinogenesis. To date, many case-control studies have investigated the association between MTHFR C677T polymorphism and colorectal cancer risk. However, the results were inconsistent. In order to derive a more precise estimation of the association, we conducted this meta-analysis. This meta-analysis recruited 61 published studies which were selected by a search of PubMed up to 31st September 2011, including 16,111 colorectal cancer cases and 23,192 controls. We used crude odds ratios (ORs) with 95?% confidence intervals (CIs) to assess the association between MTHFR C677T polymorphism and colorectal cancer susceptibility. Our results showed that MTHFR C667T polymorphism contributed to the decreased colorectal cancer risk in overall population (for TT vs. CC: OR?=?0.89, 95?% CI?=?0.82-0.97; for TT vs. CT/CC: OR?=?0.88, 95?% CI?=?0.83-0.92). In subgroup analysis by ethnicity, the results also indicated a correlation between the T allele of MTHFR C667T and the colorectal cancer risk in Asian population (for TT vs. CC: OR?=?0.82, 95?% CI?=?0.69-0.97; for TT vs. CT/CC: OR?=?0.81, 95?% CI?=?0.74-0.90). Additionally, the correlation was also observed in male subgroup in sub-analysis by gender (for TT vs. CC: OR?=?0.82, 95?% CI?=?0.71-0.93; for TT vs. CT/CC: OR?=?0.81, 95?% CI?=?0.71-0.92). In summary, our meta-analysis strongly indicated the MTHFR C667T polymorphism was associated with a reduced risk of CRC.     

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.