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MTHFR 677C>T polymorphism increases the male infertility risk: a meta-analysis involving 26 studies.

Gong M, Dong W, He T, Shi Z, Huang G, Ren R, Huang S, Qiu S, Yuan R - PLoS ONE (2015)

Bottom Line: CC: OR = 1.34, 95% CI: 1.23-1.46) and random effects models (CT+TT vs.CC: OR = 1.39, 95% CI: 1.19-1.62).Nevertheless, no significant association was only observed in oligo subgroup.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, China; Department of Andrology, Zhongshan Affiliated Hospital of Sun Yat-sen University, Zhongshan, Guangdong, 528403, China.

ABSTRACT

Background and objectives: Methylenetetrahydrofolate reductase (MTHFR) polymorphism may be a risk factor for male infertility. However, the epidemiologic studies showed inconsistent results regarding MTHFR polymorphism and the risk of male infertility. Therefore, we performed a meta-analysis of published case-control studies to re-examine the controversy.

Methods: Electronic searches of PubMed, EMBASE, Google Scholar and China National Knowledge Infrastructure (CNKI) were conducted to select eligible literatures for this meta-analysis (updated to June 19, 2014). According to our inclusion criteria and the Newcastle-Ottawa Scale (NOS), only high quality studies that observed the association between MTHFR polymorphism and male infertility risk were included. Crude odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of association between the MTHFR polymorphism and male infertility risk.

Results: Twenty-six studies involving 5,575 cases and 5,447 controls were recruited. Overall, MTHFR 677C>T polymorphism showed significant associations with male infertility risk in both fixed effects (CT+TT vs. CC: OR = 1.34, 95% CI: 1.23-1.46) and random effects models (CT+TT vs. CC: OR = 1.39, 95% CI: 1.19-1.62). Further, when stratified by ethnicity, sperm concentration and control sources, the similar results were observed in Asians, Caucasians, Azoo or OAT subgroup and both in population-based and hospital-based controls. Nevertheless, no significant association was only observed in oligo subgroup.

Conclusions: Our results indicated that the MTHFR polymorphism is associated with an increased risk of male infertility. Further well-designed analytical studies are necessary to confirm our conclusions and evaluate gene-environment interactions with male infertility risk.

No MeSH data available.


Related in: MedlinePlus

Flow diagram of study selection.
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pone.0121147.g001: Flow diagram of study selection.

Mentions: Through a literature searching, initially a total of 46 potentially relevant publications were indentified. Out of these, eleven studies were eliminated because they did not investigate the association between the MTHFR 677C>T polymorphism and male infertility risk. After data extraction, we excluded 4 articles from the meta-analysis. One of them had no controls [26] while one of them had no cases [27], besides, the other two studies were excluded as one did not provide detailed information needed for OR calculation [28] while the last one did not directly research about the genotype and male infertility risk [29]. Hence, we obtained 31 relevant articles that examined the association between MTHFR 677C>T and male infertility risk. Among of them, five studies were excluded because of the poor quality, which was evaluated by Newcastle-Ottawa Scale [30–34]. Therefore, only 26 studies qualifying our strict selection criteria were involved in the meta-analysis [11, 16, 19, 35–57] (Fig. 1). We established a database of the extracted information from each eligible article (Table 1). The total data for this analysis included 5,575 cases and 5,447 controls for MTHFR 677C>T polymorphism. All the researches contained in this meta-analysis are case-control studies. Of the 26 studies included in the meta-analysis, there were 10 studies of Asians, 11 studies of Caucasians, 1 study of African and 4 studies did not mention. According to the control sources, general populations were used as controls in 12 studies whereas hospital patients were used in 8 studies and 6 studies did not mention. The genotype distributions among the controls of all studies followed HWE except for two studies [37, 49].


MTHFR 677C>T polymorphism increases the male infertility risk: a meta-analysis involving 26 studies.

Gong M, Dong W, He T, Shi Z, Huang G, Ren R, Huang S, Qiu S, Yuan R - PLoS ONE (2015)

Flow diagram of study selection.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4368707&req=5

pone.0121147.g001: Flow diagram of study selection.
Mentions: Through a literature searching, initially a total of 46 potentially relevant publications were indentified. Out of these, eleven studies were eliminated because they did not investigate the association between the MTHFR 677C>T polymorphism and male infertility risk. After data extraction, we excluded 4 articles from the meta-analysis. One of them had no controls [26] while one of them had no cases [27], besides, the other two studies were excluded as one did not provide detailed information needed for OR calculation [28] while the last one did not directly research about the genotype and male infertility risk [29]. Hence, we obtained 31 relevant articles that examined the association between MTHFR 677C>T and male infertility risk. Among of them, five studies were excluded because of the poor quality, which was evaluated by Newcastle-Ottawa Scale [30–34]. Therefore, only 26 studies qualifying our strict selection criteria were involved in the meta-analysis [11, 16, 19, 35–57] (Fig. 1). We established a database of the extracted information from each eligible article (Table 1). The total data for this analysis included 5,575 cases and 5,447 controls for MTHFR 677C>T polymorphism. All the researches contained in this meta-analysis are case-control studies. Of the 26 studies included in the meta-analysis, there were 10 studies of Asians, 11 studies of Caucasians, 1 study of African and 4 studies did not mention. According to the control sources, general populations were used as controls in 12 studies whereas hospital patients were used in 8 studies and 6 studies did not mention. The genotype distributions among the controls of all studies followed HWE except for two studies [37, 49].

Bottom Line: CC: OR = 1.34, 95% CI: 1.23-1.46) and random effects models (CT+TT vs.CC: OR = 1.39, 95% CI: 1.19-1.62).Nevertheless, no significant association was only observed in oligo subgroup.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, China; Department of Andrology, Zhongshan Affiliated Hospital of Sun Yat-sen University, Zhongshan, Guangdong, 528403, China.

ABSTRACT

Background and objectives: Methylenetetrahydrofolate reductase (MTHFR) polymorphism may be a risk factor for male infertility. However, the epidemiologic studies showed inconsistent results regarding MTHFR polymorphism and the risk of male infertility. Therefore, we performed a meta-analysis of published case-control studies to re-examine the controversy.

Methods: Electronic searches of PubMed, EMBASE, Google Scholar and China National Knowledge Infrastructure (CNKI) were conducted to select eligible literatures for this meta-analysis (updated to June 19, 2014). According to our inclusion criteria and the Newcastle-Ottawa Scale (NOS), only high quality studies that observed the association between MTHFR polymorphism and male infertility risk were included. Crude odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of association between the MTHFR polymorphism and male infertility risk.

Results: Twenty-six studies involving 5,575 cases and 5,447 controls were recruited. Overall, MTHFR 677C>T polymorphism showed significant associations with male infertility risk in both fixed effects (CT+TT vs. CC: OR = 1.34, 95% CI: 1.23-1.46) and random effects models (CT+TT vs. CC: OR = 1.39, 95% CI: 1.19-1.62). Further, when stratified by ethnicity, sperm concentration and control sources, the similar results were observed in Asians, Caucasians, Azoo or OAT subgroup and both in population-based and hospital-based controls. Nevertheless, no significant association was only observed in oligo subgroup.

Conclusions: Our results indicated that the MTHFR polymorphism is associated with an increased risk of male infertility. Further well-designed analytical studies are necessary to confirm our conclusions and evaluate gene-environment interactions with male infertility risk.

No MeSH data available.


Related in: MedlinePlus