Relevance of KISS1 gene polymorphisms in susceptibility to Polycystic Ovary Syndrome and its associated Endocrine and Metabolic disturbances.

Background: Variations in KISS1 gene have been postulated as an emerging genetic factor in polycystic ovary syndrome (PCOS) susceptibility. Likewise, the multifactorial etiology of PCOS is associated with the involvement of disturbances in endocrine and metabolic systems.Aims: The present study aims to investigate the relevance of KISS1 gene polymorphisms in PCOS and its associated endocrine and metabolic disturbances.Methods: The study included 104 PCOS women and 109 controls. Endocrine (kisspeptin, LH, FSH, LH-FSH ratio, estradiol) and metabolic (cholesterol, triglycerides, HDL, LDL, insulin and glucose) parameters were measured in the study groups. PCR and nucleotide sequencing were carried out to screen single nucleotide polymorphisms (SNPs) of KISS1 gene. Levels of endocrine and metabolic parameters of PCOS women were compared in the genotypes.Results: Endocrine and metabolic disturbances were reflected as significantly higher levels of LH, LH-FSH ratio, estradiol, cholesterol, triglycerides, LDL, insulin and glucose in PCOS women than controls. Three novel SNPs (rs1213704663C>G, rs1481572212T>G and rs775770652G>A) were detected in KISS1 gene. Of these SNPs, the genotype and allele frequencies of rs1213704663C>G were significantly associated (CG: p=0.0004, GG: p=0.0006, mutant-G: p=0.00001) with PCOS. The LH and estradiol hypersecretion, and increased LH-FSH ratio of PCOS women were significantly influenced by the GG genotype of rs1213704663. Interestingly, this SNP showed no influence on kisspeptin level. The other two SNPs rs1481572212T>G and rs775770652G>A exhibited no clinical significance.Conclusion: Women having rs1213704663C>G variation in KISS1 gene are highly susceptible to PCOS and its associated endocrine and metabolic disturbances (LH and estradiol hypersecretion, and increased LH/FSH).Keywords: Polycystic ovary syndrome, gene polymorphisms, Metabolic and Endocrine disturbances, LH, estradiol.