Association of Calpain10 polymorphisms with polycystic ovarian syndrome susceptibility: a systematic review and meta-analysis with trial sequential analysis

Abstract

Insulin resistance plays an important role in the pathogenesis of polycystic ovarian syndrome (PCOS). Calpain10 (CAPN10) gene was the first identified susceptibility gene for type 2 diabetes mellitus and closely related to insulin sensitivity. A lot of research attention has been attracted on the relationship between CAPN10 polymorphisms and PCOS risk, but they didn’t reach a consistent conclusion. We therefore performed this systematic review and meta-analysis to assess the association of CAPN10 common variants with PCOS susceptibility. A total of 21 studies were eligible for inclusion. Meta-analyses were done for 5 variants that had at least two data sources: UCSNP-19, -43, −44, −56 and −63. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under five genetic models. Subgroup analyses by ethnicity, PCOS diagnostic criteria, and source of controls were conducted. Moreover, false-positive report probability (FPRP) test and trial sequential analysis (TSA) were performed to assess the significant associations. The results showed a possible negative association between UCSNP-19 and PCOS risk (ins/ins vs. del/del + del/ins: OR = 0.84, 95% CI: 0.72–0.98). In subgroup analyses, FPRP test indicated that noteworthy associations were observed in mixed ethnicities for UCSNP-43 (A vs. G: OR = 1.81, 95% CI: 1.17-2.79; AA + AG vs. GG: OR = 2.14, 95% CI: 1.20-3.80) and in Asians for UCSNP-44 (CC vs. TT: OR = 2.07, 95% CI: 1.21-3.51; CC vs. CT + TT: OR = 2.19, 95% CI: 1.31-3.69), but TSA plots showed that the accumulated sample sizes of these associations were insufficient to draw firm conclusions. In summary, our study suggested that UCSNP-19, UCSNP-43, and UCSNP-44 in CAPN10 gene may be involved in PCOS susceptibility. These findings warrant further studies.