Influence of KISS1 gene polymorphisms on the risk of polycystic ovary syndrome and its associated variables, in Saudi women.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex multifactorial disorder, affecting millions of women worldwide. The role of genetic polymorphisms of the KISS1 gene on the development of PCOS is still obscure. This study was designed to investigate the probable influence of KISS1 gene polymorphisms on PCOS and its associated variables: BMI, waist-hip ratio, kisspeptin, LH, FSH, and LH-FSH ratio. METHODS: The study comprised 104 PCOS women and 109 controls, with age ranging from 19 to 36 years. BMI, waist-hip ratio, and circulating levels of kisspeptin, LH, and FSH were measured. DNA was extracted, and genotyping of the KISS1 gene was carried out by nucleotide sequencing. The PCOS-associated variables were analyzed in different genotypes of single nucleotide polymorphisms (SNPs) of the KISS1 gene. RESULTS: The values of waist-hip ratio (WHR), LH, and LH-FSH ratio were significantly higher in PCOS women than controls. BMI, kisspeptin, and FSH levels exhibited no significant difference between the groups. Six novel SNPs of KISS1 gene were identified. Three: rs372790354G > A, rs12998G > A, and rs35431622A > T were investigated. Among these SNPs, the genotype and allele frequencies of rs372790354 showed significant association with PCOS (GA: p = 0.018, AA: p = 0.022, mutant allele-A: p = 0.021) and the G allele was protective. The values of LH, kisspeptin, and WHR of PCOS women were significantly influenced (p < 0.05) by the AA genotype of rs372790354. The other two SNPs rs12998G > A and rs35431622A > T revealed no significant influence on PCOS and associated variables. Haplotypes were constructed, but there was no significant difference between the patients and controls. CONCLUSION: In conclusion, this is the first study, which reports a significant influence of KISS1 gene polymorphism (rs372790354G > A) on PCOS and its associated variables. However, more extensive research is necessary to confirm these findings.

rs4889 polymorphism in KISS1 gene, its effect on polycystic ovary syndrome development and anthropometric and hormonal parameters in Saudi women.

BACKGROUND: Kisspeptin is involved in female reproduction. This study was designed to i- estimate kisspeptin levels in women with polycystic ovary syndrome (PCOS), in comparison with controls, ii- study the correlations between kisspeptin and PCOS-related reproductive hormones, and iii- investigate the relation between KISS1 gene polymorphisms and hormone levels in women suffering from PCOS. METHODS: The investigation was a clinically designed study on 28 women with PCOS, and 30 normal, healthy women with no signs of PCOS as controls. Blood samples were collected between day 3 and day 6 of the menstrual cycle in both groups at 8:00 a.m., and circulating levels of LH, FSH and kisspeptin were estimated. DNA was extracted from whole blood and all coding exons of KISS1 gene were sequenced. RESULTS: Women with PCOS had higher LH levels and BMI compared to controls. Plasma kisspeptin levels were positively correlated with LH levels. There was no statistically significant difference between the groups in terms of kisspeptin and FSH levels. The SNP rs4889 C/G, a non-synonymous SNP, was investigated in the PCOS group. The frequency of GG genotype was significantly higher in the PCOS compared to the controls. These patients were more obese, had higher kisspeptin and FSH levels. CONCLUSION: The results of the study show that the genetic variation of KISS1 gene may be a factor contributing to PCOS development. The association between the gene and the gene variation and PCOS need further validation in large-scaled and functional studies.