تأثير تعدد الأشكال الجيني KISS1 على تطور متلازمة تكيس المبايض لدى النساء العراقيات

The effect of KISS1 gene polymorphism on development of polycystic ovary syndrome in Iraqi women

Abstract

Background: Polycystic ovarian syndrome (PCOS) is a multifactorial illness that affects millions of women around the world. Kisspeptin is involved in the control of human reproduction bridging the gap between the sex steroid levels and feedback mechanisms that control the gonadotropin releasing hormone (GnRH) secretion; however, studies considering this peptide and infertility are limited. It’s yet unclear what effect may play the genetic variants in the KISS1 gene in the development of PCOS.
Kisspeptin is a neuropeptide that stimulates the production of gonadotropin-releasing hormone (GnRH). It is required for the rise of Luteinizing Hormone (LH), Follicular stimulating hormone (FSH), and ovulation. This neuropeptide is necessary for normal reproductive function and the onset of puberty. Both GnRH and LH secretion are altered in women with polycystic ovarian syndrome (PCOS). This study aimed to study the genetic polymorphism of KISS1 gene and its effect on women with polycystic ovary syndrome development.
Subjects, Materials and Methods: The present work included a case control study for a group of 105 subjects (16 obese with PCOS, 19 overweight with PCOS, 35 normal weight with PCOS and 35 apparently healthy women as control group) were selected from the Infertility Department/ Gynaecology and Obstetrics Teaching Hospital in Karbala and from out clinic patients. Blood samples were collected from patients and control and each sample was divided into two parts used for genetic and serum analysis. Genetic polymorphism was performed for KISS1 gene and Enzyme Link Immunosorbent Assay system (ELISA) was performed using sandwich method to measure the concentrations of serum Human kisspeptin 1as well as, hormonal analysis.
Results: the study ҆s results indicated that primary infertility, irregular menstrual cycle, hirsutism, acne and hair loss were associated with both obese and non-obese PCOS groups. The Kisspeptin levels, LH, FSH, free Testosterone and prolactin were higher significantly in both obese and non-obese PCOS groups compared to control. Kisspeptin level was correlated positively with early Age (18-23years) in overweight PCOS group. The nonsynonymous SNP rs4889 (C/G) was found more frequently in the obese women with PCOS than in the overweight and normal weight women with PCOS and control groups. Allele C showed higher frequency in obese women with PCOS (31.2%) than overweight and normal weight women with PCOS (26.3%) and (28.5%) respectively, and control group (14.2%). The frequency of heterozygous allele (GC) was twice folds higher in PCOS cases than in controls. The homozygous genotypes (CC) were found just in PCOS with normal weight.
Conclusion: This study found the non-synonymous SNP rs4889 (C/G) more frequently in the obese women with PCOS than in the overweight and normal weight women with PCOS and control groups, and this SNP causes P81R substitution. And it has been observed that the allele frequency GG is statistically significant between the four groups (three of PCOS groups and control) in FSH, LH/FSH ratio, free testosterone and Kisspeptin1. While, the GC allele showed significant difference with LH, FSH, LH/FSH ratio between the four groups (three of PCOS groups and control). The significant difference was appeared in serum kisspeptin1 levels between PCOS groups as compared with control group. No significant correlations were found in other biochemical parameters.