The KISS1R gene rs350132 variant is significantly associated with central precocious puberty susceptibility among Asian girls: evidence from a case-control study and a meta-analysis

Purpose: It is widely known that kisspeptin receptor (KISS1R) plays central regulatory roles in the hypothalamus-pituitary-gonad (HPG) axis, whose premature activation has been implicated in the pathogenesis of central precocious puberty (CPP). The aim of our present study was to verify the contributions of the three most examined KISS1R gene variants (rs184749, rs350132, and rs3746146) to pubertal timing. Methods: Sanger sequencing was applied to genotype the KISS1R gene variants in 422 healthy girls and 384 CPP girls, all from Hubei province. Moreover, the data from previous related studies and present study were integrated and meta-analyzed. Results: The case-control study revealed that rs184749 G allele (P=0.004, OR=1.42, 95%CI=1.12-1.79) and rs350132 A allele (P=0.007, OR=1.38, 95%CI=1.09-1.75) acted as the risk factors for CPP susceptibility, and haplotype GAC carrying the rs184749 (G) and rs350132 (A) was associated with an increased CPP risk among Hubei Chinese girls (P=0.005, OR=1.44, 95%CI=1.12-1.86). The subsequent meta-analysis confirmed the effect of rs350132 on CPP susceptibility in Asian girls under the genetic models of A vs. T and AA vs. AT+TT. The expression quantitative trait loci (eQTL) analysis revealed that KISS1R gene mRNA is differentially expressed in clinical tissues across rs350132 genotypes. Conclusion: The present findings suggested that the KISS1R gene rs350132 may serve as a susceptible locus in CPP pathogenesis among Asian girls, which warrants confirmation and reinforcement in future studies.