Decoding the KISS1 gene: unraveling KISS1 polymorphisms in the pathogenesis of polycystic ovarian syndrome (PCOS)

Abstract

Abstract Background Polycystic ovarian syndrome (PCOS) is a common endocrine disorder and the leading cause of anovulatory infertility in women of reproductive age. Changes in the pulsatility of hypothalamic gonadotropin-releasing hormone (GnRH) have been linked to the pathophysiology of PCOS. Kisspeptin, a neuropeptide encoded by the KISS1 gene, plays a crucial role in regulating GnRH secretion and has emerged as a potential factor contributing to reproductive dysfunction associated with PCOS. Main body This review aims to evaluate the association between KISS1 gene polymorphisms and hormone profiles in women with PCOS across different populations. A comprehensive literature search was conducted to identify original studies examining KISS1 gene variants and kisspeptin levels in patients with PCOS. Eligible articles were selected based on predefined inclusion criteria.The analysis identified several KISS1 polymorphisms—most notably rs4889 C>G, rs372790354 G > A , rs12998 G > A , and rs587777844 —associated with PCOS susceptibility, hormonal dysregulation (including elevated luteinizing hormone, testosterone, and altered LH/FSH ratios), and metabolic markers. Among these, rs4889 was the most frequently studied variant, reported across multiple populations, including Saudi Arabia, Iraq, Sri Lanka, and China. Population-specific differences were noted in the distribution and significance of individual SNPs, suggesting possible ethnic variation in genetic risk. Kisspeptin levels were also variably associated with reproductive hormones such as Anti-Müllerian Hormone and estradiol, but less consistently with metabolic markers like insulin and HOMA-IR. Conclusion KISS1 gene polymorphisms, particularly rs4889, may contribute to the complex, multifactorial etiology of PCOS through their regulatory effects on reproductive hormones. Further large-scale, phenotype-stratified, and functionally validated studies are warranted to confirm these associations and explore their clinical utility in the diagnosis and management of PCOS.