CAG-repeat variant in the polymerase γ gene and male infertility in the Chinese population: a meta-analysis

Abstract

Several studies have reported a relationship between the length of the CAG-repeat in the polymerase γ (POLG) gene and male infertility. However, other studies have not reproduced this result. In our study, the POLG-CAG-repeat length was analyzed in 535 healthy individuals from six Chinese Han populations living in different provinces. The frequencies of 10-CAG alleles and genotypes were high (97.38 and 94.13%, respectively), with no significant difference among the six Chinese Han populations. Furthermore, we determined the distribution of the POLG-CAG-repeat in 150 infertile men and 126 fertile men. Our study suggested that the distributions of POLG-CAG-repeat alleles and genotypes were not significantly different between infertile (95.67 and 92.67%, respectively) and fertile men (97.22 and 94.44%, respectively). In a subsequent meta-analysis, combining our data with data from previous studies, a comparison of the CAG-repeat alleles in fertile versus infertile men showed no obvious risk for male infertility associated with any particular allele (pooled odds ratio (OR)=0.94; 95% confidence interval (CI): 0.60-1.48). The significance level was not attained with any of the following genetic models: homozygote comparison (not 10/not 10 versus 10/10: OR=1.34; 95% CI: 0.66-2.72), heterozygote comparison (10/not 10 versus 10/10: OR=1.04; 95% CI: 0.78-1.38), dominant model comparison (not 10/not 10+10/not 10 versus 10/10: OR=1.08; 95% CI: 0.79-1.47) and recessive genetic comparison (not 10/not 10 versus 10/not 10+10/10: OR=1.31; 95% CI: 0.68-2.55). In conclusion, there is no significant difference of the frequencies of POLG-CAG-repeat variants among six Chinese Han populations, and this polymorphism may not be associated with Chinese male infertility. On the basis of a meta-analysis, there is no obvious association between CAG-repeat variants of the POLG gene and male infertility.

Figure 1

Meta-analysis with a random effects model for the ORs of male infertility risk associated with CAG-repeat variant alleles (not 10 versus 10). CI, confidence interval; OR, odds ratio.

Figure 2

Pooled odds ratios of male infertility by different genetic model comparisons. (a) The heterozygote comparison (10/not 10 versus 10/10); (b) the homozygote comparison (not 10/not 10 versus 10/10); (c) the dominant model comparison (not 10/not 10+10/not 10 versus 10/10); (d) the recessive genetic comparison (not 10/ not 10 versus 10/not 10+10/10). CI, confidence interval.

Figure 3

Sensitivity analysis of this meta-analysis. The vertical axis indicates the log odds ratio of the POLG-CAG-repeat variant that has been estimated. The meta-analysis is dominated by the Rovio et al.'s study; hence omission of other studies makes little or no difference. If the observation made by Rovio et al. is omitted, then there appears a clear result that the POLG-CAG-repeat variant is not associated with male infertility. POLG, polymerase γ.

Figure 4

Funnel plot for publication bias of the meta-analysis of male infertility risk and CAG-repeat variant of POLG gene (dominant model comparison: not 10/not 10+10/not 10 versus 10/10). POLG, polymerase γ.