KISS1 gene polymorphism in Korean girls with central precocious puberty
중추성 성조숙증을 가진 한국 여아에서 KISS1 유전자 다형성
Dept. of Medicine/박사
Kisspeptin and G-protein coupled receptor-54 (GPR54) system is the essential gatekeeper of the reproductive system, playing a key role in the activation of the gonadotropic axis at puberty. Central precocious puberty (CPP) is caused by the premature activation of hypothalamic gonadotropin-releasing hormone secretion. Recently, an activationg mutation of GPR54 gene was identified in a girl with CPP, implicating the kisspeptin system in the pathogenesis of sexual precocity. Because of the important function of kisspeptin in the regulation of puberty onset, alterations in KISS1 gene might contribute to the pathogenesis of CPP, as well as GPR54 gene. This study was aimed to evaluate the occurrence of sequence variations, including mutations and single-nucleotide polymorphisms (SNP) of KISS1 gene and attempted to clarify the effect of each sequence variation that differed in frequencies between Korean girls with CPP and their controls by investigating serum kisspeptin levels. All coding exons of KISS1 gene were sequenced in 143 Korean girls with CPP and 101 their controls. Serum kisspeptin levels of CPP (n=40) and control (n=40) groups were assayed with a competitive enzyme immunoassay. Nine polymorphisms were identified in KISS1 gene. A novel SNP, 55648176 T/G was identified for the first time. SNP 55648184 C/G and 55648186 -/T were detected more frequently in CPP group compared to control group. Moreover, subjects with these polymorphisms had higher serum kisspeptin levels than subjects lacking them. SNP 55648176 T/G was detected less frequently in CPP group compared to control group and subjects with these polymorphisms had lower serum kisspeptin levels than subjects lacking them. In total, 21 haplotypes were constructed based on the typing results. Haplotype GGGC-ACCC was detected less frequently in CPP group and seems to exert a protective effect on CPP. This study has found a novel SNP and identified three SNPs with significant differences in allele frequencies with the clinical significance of these polymorphisms. The association between SNPs and CPP should be validated by further evidence obtained from large-scaled studies. Efforts to identify other ligands activating GPR54 instead of kisspeptin are also needed.