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

Yamei Li; Ting Han; Yingxia Wang; Jie Gao; Jianglin Zhang; Yinglan Wu; Jiayou Luo

doi:10.3389/fgene.2023.1153960

September 1, 2023Frontiers in GeneticsOpen Access

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

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Why the study?

Studies assessing the relationship between Calpain10 (CAPN10) gene polymorphisms and polycystic ovarian syndrome (PCOS) risk had yielded inconsistent conclusions.

Are CAPN10 polymorphisms associated with polycystic ovarian syndrome susceptibility?

Structured PICO

Are CAPN10 polymorphisms associated with polycystic ovarian syndrome susceptibility?

P

Population

21 studies assessing the association of CAPN10 common variants with polycystic ovarian syndrome (PCOS) susceptibility

I

Intervention

CAPN10 polymorphisms (UCSNP-19, -43, -44, -56, and -63)

C

Comparator

Other alleles/genotypes

O

Outcome

Polycystic ovarian syndrome (PCOS) susceptibility/risk

CAPN10 polymorphisms UCSNP-19, -43, and -44 may be associated with PCOS susceptibility, but current evidence is underpowered to draw definitive conclusions.

Limitations

insufficient accumulated sample sizes to draw firm conclusions based on trial sequential analysis

Implication

Does not support CAPN10 genotyping for PCOS risk assessment; leaves open confirmation of any association with larger powered studies.

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.