Polymorphisms in estrogen receptors predict the risk of male infertility: a meta-analysis

Abstract

Background: Estrogen receptors play an important role in mediating estrogen action on target tissues, and the estrogen is relevant to male infertility. Single nucleotide polymorphisms (SNPs) in estrogen receptors may be associated with the risk of male infertility. A variety of case control studies have been published evaluating this association. However, the accumulated studies have shown inconsistent conclusions.

Methods: To further determine the potential association between the four common SNPs (rs2234693, rs9340799, rs1256049 and rs4986938) in estrogen receptors gene and male infertility, this meta-analysis was performed according to the 10 published case control studies. The odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the strength of the associations.

Results: It was revealed that the sub-group analysis by the ethnicity, for the rs2234693, a significant association in the comparison of CC vs. TT (OR = 0.61, 95% CI: 0.40-0.93), CT vs. TT (OR = 0.67, 95% CI: 0.49-0.93) and CC + CT vs. TT (OR = 0.66, 95% CI: 0.49-0.89) in the Asian population with male infertility. For rs9340799 polymorphism, increased risks were observed for the comparison of AA vs. GG (OR = 1.75, 95% CI: 1.15-2.68) and AA vs. GA + GG (OR = 1.38, 95% CI: 1.02-1.88). For rs1256049 polymorphism, the comparison of the GA vs. GG (OR = 1.52, 95% CI: 1.00-2.31) and AA + GA vs. GG (OR = 1.74, 95% CI: 1.03-2.94), also increased risks present in Asian and Caucasian population, respectively.

Conclusions: The rs2234693C allele was associated with the decreased risk for male infertility; however, the rs9340799AA genotype and the rs1256049GA genotype were associated with an increased risk for male infertility.

Figure 1

Flow chart of studies identified with inclusion and exclusion criteria.

Figure 2

The allel frequencies of the four polymorphisms in the controls may vary by ethnicity. (A) rs2234693, (B) rs9340799, (C) rs1256049, (D) rs4986938. Star or dot denotes outliers.

Figure 3

Forest plot for the overall association between rs1256049 polymorphism and male infertility for random effects. For GA vs. GG each study was shown by the point estimate of the OR (the size of the square is proportional to the weight of each study) and 95% CI for the OR (extending lines); the pooled OR and 95% CI were shown by diamonds.

Figure 4

Begg’s funnel plot of publication bias test for the rs1256049. (A) GA vs. GG. (B) AA + GA vs. GG. Each point represents a separate study for the indicated association. Log (OR), natural logarithm of OR. Horizontal line means effect size.

Figure 5

Begg’s funnel plot of publication bias test for the rs1256049 using the trim-and-fill method. (A) GA vs. GG. (B) AA + GA vs. GG. Each point represents a separate study for the indicated association. Log (OR), natural logarithm of OR. Horizontal line means effect size. The adjusted estimates obtained by using the random effects model for GA vs. GG and AA + GA vs. GG.