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GSTM1 and GSTT1 null polymorphisms and male infertility risk: an updated meta-analysis encompassing 6934 subjects.

ABSTRACT: Published data on the association between the GST genes polymorphisms and male infertility risk are inconclusive. We investigated GST genes polymorphisms in a large sample size case-control study, and conducted a literature-based meta-analysis of 6934 individuals. Our case-control study showed the GSTM1 null genotype was significantly associated with idiopathic oligozoospermia, while the null genotype of GSTT1 was significantly associated with normozoospermia and azoospermia. Additionally, significantly elevated GSTT1 expression levels were observed in present genotype compared with null genotype. In the meta-analysis, the null genotype of GSTM1 was associated with a significantly increased risk of male infertility. Furthermore, a stratification analysis showed that the risk of GSTM1 polymorphism was associated with male infertility in both Asian and Caucasian groups. Further studies of GSTM1 and GSTT1 with their biological functions are needed to understand the role of these genes in the development of male infertility.

SUBMITTER: Wu W

PROVIDER: S-EPMC6505401 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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GSTM1 and GSTT1 null polymorphisms and male infertility risk: an updated meta-analysis encompassing 6934 subjects.

Wu Wei W Lu Jing J Tang Qiuqin Q Zhang Simin S Yuan Beilei B Li Jing J Di Wu Sun Hong H Lu Chuncheng C Xia Yankai Y Chen Daozhen D Sha Jiahao J Wang Xinru X

Scientific reports 20130101

Published data on the association between the GST genes polymorphisms and male infertility risk are inconclusive. We investigated GST genes polymorphisms in a large sample size case-control study, and conducted a literature-based meta-analysis of 6934 individuals. Our case-control study showed the GSTM1 null genotype was significantly associated with idiopathic oligozoospermia, while the null genotype of GSTT1 was significantly associated with normozoospermia and azoospermia. Additionally, signi ...[more]

PMID: 23877133

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Project description:Preventing the ototoxicity caused by cisplatin is a major issue yet to be overcome. Useful preventive treatments will soon be available. Consequently, the next step is to filter out those patients who are more prone to develop ototoxicity. The aim of this study was to prospectively evaluate potential predictive markers of acute ototoxicity as determined by measures of distortion product otoacoustic emissions (DPOAEs). A total of 118 patients from our previous DPOAE analysis were put under evaluation. Ototoxic cases were divided according to unilateral (n = 45) or bilateral (n = 23) involvement. The clinicopathological characteristics, hearing test results, germline GSTT1, GSTM1, and GSTP1 polymorphisms, and common laboratory parameters were included in the new analysis. Univariate and multivariate statistical tests were applied. According to multivariate logistic regression, the only independent predictor of unilateral ototoxicity (vs. non-affected) was a GSTM1 null genotype (OR = 4.52; 95%CI = 1.3-16.3), while for bilateral damage, the GSTT1 null genotype (OR = 4.76; 1.4-16) was a predictor. The higher starting serum urea level was characteristic of bilateral ototoxicity; however, the only independent marker of bilateral (vs. unilateral) ototoxicity was the presence of GSTT1 null genotype (OR = 2.44; 1.23-4.85). Different processes, involving the GSTM1 and GSTT1 genotypes, respectively, govern the development of acute unilateral and bilateral ototoxicities. Further research is needed to clarify these processes. Based on the above findings, patients whom are at risk may be selected for otoprotective therapies. KEY MESSAGES: The acute ototoxicity was determined by DPOAE in 118 testicular cancer patients. GSTM1 null was the only marker of unilateral ototoxicity (vs. non-affected). The only marker of bilateral hearing loss (vs. non-affected) was the GSTT1 null. GSTT1 null was also the marker of bilateral vs. unilateral ototoxicity. A high-risk group may be selected for new, individualized otoprotective treatment.

Project description:Background18 previous meta-analyses have been published on the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms with male infertility risk. However, results of the previous meta-analyses were still inconsistent. Moreover, their meta-analyses did not assess false-positive report probabilities except one study. Furthermore, many new studies have been published, and therefore an updated meta-analysis and re-analysis of systematic previous meta-analyses were performed to further explore these issues.ObjectivesTo determine the association between MTHFR C677T and A1298C polymorphisms and male infertility risk.MethodsCrude odds ratios and their 95% confidence intervals were used to assess the association between MTHFR C677T and A1298C polymorphisms and male infertility risk. We used the Bayesian false discovery probability (BFDP) to assess the credibility of statistically significant associations.ResultsFifty-nine studies were included concerning the MTHFR C677T and 28 studies were found on the MTHFR A1298C with male infertility risk. Overall, the MTHFR C677T was associated with increased male infertility risk in overall populations, Africans, East Asians, West Asians, South Asians, azoospermia, and Oligoasthenoteratozoospermia (OAT). In further sensitivity analysis and BFDP test, the positive results were only considered as "noteworthy" in the overall population (TT vs CC: BFDP =?0.294, CT + TT vs CC: BFDP =?0.300, T vs C: BFDP =?0.336), East Asians (TT vs CC: BFDP =?0.089, TT vs CT + CC: BFDP =?0.020, T vs C: BFDP?<?0.001), West Asians (TT vs CC: BFDP =?0.584), hospital-based studies (TT vs CC: BFDP =?0.726, TT vs CT + CC: BFDP =?0.126), and OAT (TT vs CT + CC: BFDP =?0.494) for MTHFR C677T. In addition, a significantly increased male infertility risk was found in East Asians and population-based studies for MTHFR A1298C. However, we did not find that the positive results were considered as "noteworthy" in the overall and all subgroup analyses for MTHFR A1298C.ConclusionsIn summary, this study indicates that the MTHFR C677T is associated with increased male infertility risk in East Asians, West Asians, and OAT. No significant association was observed on the MTHFR A1298C with male infertility risk.

Project description:BACKGROUND AND OBJECTIVES: The GSTM1, GSTT1 and GSTP1 polymorphisms might be involved in inactivation of procarcinogens that contribute to the genesis and progression of cancers. However, studies investigating the association between GSTM1, GSTT1 or GSTP1 polymorphisms and prostate cancer (PCa) risk report conflicting results, therefore, we conducted a meta-analysis to re-examine the controversy. METHODS: Published literature from PubMed, Embase, Google Scholar and China National Knowledge Infrastructure (CNKI) were searched (updated to June 2, 2012). According to our inclusion criteria, studies that observed the association between GSTM1, GSTT1 or GSTP1 polymorphisms and PCa risk were included. The principal outcome measure was the odds ratio (OR) with 95% confidence interval (CI) for the risk of PCa associated with GSTM1, GSTT1 and GSTP1 polymorphisms. RESULTS: Fifty-seven studies involving 11313 cases and 12934 controls were recruited. The overall OR, which was 1.2854 (95% CI?=?1.1405-1.4487), revealed a significant risk of PCa and GSTM1 null genotype, and the similar results were observed when stratified by ethnicity and control source. Further, the more important is that the present study first reported the high risks of PCa for people who with dual null genotype of GSTM1 and GSTT1 (OR?=?1.4353, 95% CI?=?1.0345-1.9913), or who with GSTT1 null genotype and GSTP1 A131G polymorphism (OR?=?1.7335, 95% CI?=?1.1067-2.7152). But no association was determined between GSTT1 null genotype (OR?=?1.102, 95% CI?=?0.9596-1.2655) or GSTP1 A131G polymorphism (OR?=?1.0845, 95% CI?=?0.96-1.2251) and the PCa risk. CONCLUSIONS: Our meta-analysis suggested that the people with GSTM1 null genotype, with dual null genotype of GSTM1 and GSTT1, or with GSTT1 null genotype and GSTP1 A131G polymorphism are associated with high risks of PCa, but no association was found between GSTT1 null genotype or GSTP1 A131G polymorphism and the risk of PCa. Further rigorous analytical studies are highly expected to confirm our conclusions and assess gene-environment interactions with PCa risk.

Dataset Information

GSTM1 and GSTT1 null polymorphisms and male infertility risk: an updated meta-analysis encompassing 6934 subjects.

Publications

GSTM1 and GSTT1 null polymorphisms and male infertility risk: an updated meta-analysis encompassing 6934 subjects.

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