Genetic association between LHCGR variants and polycystic ovary syndrome: a meta-analysis

The luteinizing hormone/choriogonadotropin receptor (LHCGR) is mapped at the 2p16.3 region, which was identified as a PCOS-susceptible locus in the first genome-wide association study (GWAS). Since then, several variants of LHCGR have been documented as susceptible loci for the development of PCOS, with striking differences due to diverse racial backgrounds. The present meta-analysis was conducted to unravel the association between LHCGR variants and PCOS.

Databases such as PubMed, PCOSkb, and Google Scholar were extensively searched to gather the relevant articles. To determine the heterogeneity, I² statistic was used followed by fixed effect and random effect models depending on the degree of heterogeneity present. Different genetic models were used to assess the association between LHCGR variants and the risk of PCOS.

Out of the six studied variants, the rs2293275 and rs12470652 did not show an association with PCOS among any genetic models. The rs13405728 showed an association with all models in the overall analysis and after stratification it was associated but only in Asians. Only the recessive and additive models were found to be significantly associated with PCOS for the rs4539842 variant in the overall analysis. The rs4953616 variant displays an association under all models with the Asian and Indian populations during sub-group analysis. For the rs7371084 variant, dominant and allele models exhibited an association with PCOS during overall and sub-group analysis; however, in later only the Asians were significantly associated.

The rs4953616 variant exhibited the risk of PCOS in Indians however served as protective against the risk in Asians. The variants rs13405728, rs4539842, and rs7371084 were found to be acting as a protective factor against the development of PCOS.