rs4889 and rs5782018 polymorphisms of KISS1 gene as genetic predisposing factor for PCOS in Indonesian women

<ns3:p> Background Dysregulation of the HPG axis in PCOS causes increased frequency and amplitude of gonadotropin-releasing hormone (GnRH) pulsatility in the hypothalamus. Single nucleotide polymorphisms (SNPs) in the KISS1 gene may be associated with altered neuroendocrine signaling in PCOS. The present study aims to evaluate the association between two <ns3:italic>KISS1</ns3:italic> polymorphisms (rs4889 and rs5780218), their haplotypes, and the odds of PCOS in Indonesian women. Methods A cross-sectional study was conducted at Yasmin Clinic, dr. Cipto Mangunkusumo General Hospital, Indonesia, involving 60 women with PCOS and 60 healthy controls. Hormonal levels were assessed using ELISA, and genomic DNA was analyzed by Sanger sequencing. Demographic data were compared using independent t-tests, and chi-square tests were used for genotype and allele frequency analysis. Results The genotypic distribution of rs4889 was significantly different between the PCOS and control groups (p&lt;0.05), where the distribution of mutant genotype GG was higher in PCOS than in control (18.3% and 1.7%, respectively). The allele distribution of rs4889 and rs5782018 KISS1 SNPs were significantly different between both groups (p&lt;0.01 and p&lt;0.05, respectively). The rs4889 polymorphism was significantly different between the PCOS and control groups for the codominant and recessive models (p&lt;0.01). Moreover, the rs5780218 polymorphism was significantly different between the PCOS and control groups for the codominant and dominant models (p&lt;0.05). From the haplotype analysis, the G-CT haplotype was significantly different, with an OR value of 2.57 (1.33–4.96, p=0.0057). Conclusions <ns3:italic>KISS1</ns3:italic> rs4889 and rs5780218 polymorphisms, as well as the G–CT haplotype, are associated with increased odds of PCOS in Indonesian women. These findings support a potential role of upstream neuroendocrine genetic variation in PCOS susceptibility; however, causal inferences cannot be drawn from this cross-sectional study. </ns3:p>