Association of polymorphisms of A260G and A386G in DAZL gene with male infertility: a meta-analysis and systemic review

Abstract

To investigate the association of single nucleotide polymorphism 260 and 386 (SNP260 and SNP386) gene with male infertility, an electronic search was performed to identify case-control studies evaluating the relationship of SNP260 or SNP386 of deleted in azoospermia-like (DAZL) and male infertility. Review Manager 5 was used to process the meta-analysis and other statistical analysis. A total of 139 records were retrieved, of which 13 case-control studies with total 2715 patients and 1835 normozoospermic men were included. SNP260 was found not to play a functional role in male oligo/azoospermia either for Caucasians or for Asians. But for SNP386, models of allele (A/G), dominant (AA/AG + GG), co-dominant (AA/AG) and super-dominant (AA + GG/AG) had a strong correlation to spermatogenic failure with related odds ratio being 0.15 (95% confidence interval [95% CI] 0.07 to 0.34, P < 0.00001), 0.16 (95% CI 0.07 to 0.35, P < 0.00001), 0.15 (95% CI 0.06 to 0.33, P < 0.00001) and 0.15 (95% CI 0.06 to 0.33, P < 0.00001), respectively. Moreover, this correlation was only found in the Chinese Han population (decreasing around 85% risk of oligo/azoospermia infertility) and not found in India, Japan, and Caucasian countries. Our analysis demonstrated that SNP260 of DAZL did not contribute to oligo/azoospermia while SNP386 was correlated to male infertility. However, this correlation was only found in China with a country-specific and ethnicity-specific manner.

Figure 1

The association of single nucleotide polymorphism 260 with male infertility. A forest plot in (a) allele model (A/G), (b) dominant model (AA/AG + GG), (c) recessive model (AA + AG/GG), (d) co-dominant model (AA/AG), (e) co-dominant model (AA/GG), (f) super-dominant model (AA + GG/AG). The association was indicated as odds ratio (OR) estimate with the corresponding 95% confidence interval (CI). The OR estimate of each study is marked with a solid black square. The size of the square represents the weight that the corresponding study exerts in the meta-analysis. The CIs of pooled estimates are displayed as a horizontal line through the diamond. OR <1 indicates increased risk of male infertility. A: wild type gene, G: mutant gene.

Figure 2

The association of single nucleotide polymorphism 386 with male infertility. A forest plot in (a) allele model (A/G), (b) dominant model (AA/AG + GG), (c) recessive model (AA + AG/GG), (d) co-dominant model (AA/AG), (e) co-dominant model (AA/GG), (f) super-dominant model (AA + GG/AG). The association was indicated as odds ratio (OR) with the corresponding 95% confidence interval (CI). The OR estimate of each study is marked with a solid black square. The size of the square represents the weight that the corresponding study exerts in the meta-analysis. The CIs of pooled estimates are displayed as a horizontal line through the diamond. OR <1 indicates increased risk of male infertility. A: wild type gene and G: mutant gene.