INFLUENCE OF SINGLE NUCLEOTIDE POLYMORPHISMS OF THE KISS1 GENE ON THE DEVELOPMENT OF ANOVULATORY INFERTILITY IN WOMEN
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Abstract
The relevance of the problem is associated with the increasing prevalence of anovulatory infertility in women and the need to improve the effectiveness of its treatment.
Objective – to study the effect of single nucleotide polymorphisms of the KISS1 gene on the level of sex hormones, regulatory peptins and the development of anovulatory infertility in women.
Materials and methods. The study involved 73 women: group I included patients with a confirmed diagnosis of anovulatory infertility and menstrual dysfunction in the form of oligomenorrhea and amenorrhea; group II (control) consisted of 28 patients who had one or more normal births with a healthy child in their anamnesis. All women were determined to have levels of luteinizing and follicle-stimulating hormones, anti-Müllerian hormone. Kisspeptin and neurokinin B levels were determined by enzyme immunoassay using special commercial kits. Genomic DNA for KISS1 genotyping was isolated from peripheral blood leukocytes using the Puregene Blood Kit (QIAGEN, Cat. No. 158389). Polymorphism was determined by nucleotide sequencing using the ABI Big Dye Terminator protocol on an ABI 3100 Avant genetic analyzer. Additionally, the following were performed: ultrasound examination of the pelvic organs, ovulation control using test strips.
Results. Direct sequencing of the KISS1 gene revealed single nucleotide polymorphisms (SNP) rs4889 – genotypes CC, CG and GG. In this case, the heterozygous genotype GC of the KISS1 gene has protective properties against anovulatory infertility, and homozygous genotypes contribute to its development. The GG and CC genotypes are associated with various forms of anovulatory infertility according to the WHO classification: the GG genotype with the hypogonadotropic form of anovulatory infertility (class 1), the CC genotype with the normogonadotropic form of anovulatory infertility (class 2).
The study of the ratios between various genotypes and the level of regulatory peptides showed a significant decrease in the kisspeptin level and an increase in the level of neurokinin B in women with the GG genotype, which does not contradict modern data on the mechanisms of their action. In addition, with the GG genotype, there is a constantly low level of gonadotropins throughout the menstrual cycle, with the CC genotype, the gonadotropin level was within the reference values.
All women included in the study had a normal ovarian reserve, confirmed by normal AMH levels. Ultrasound data confirmed the presence of anovulatory infertility in women with the GG and CC genotypes. In both cases, anovulation was confirmed by a monophasic rectal temperature curve throughout the menstrual cycle and negative FRAUTEST test data.
Conclusion. The obtained results allow us to suggest the involvement of single nucleotide polymorphisms of the KISS1 gene (GG and CC) in the development of anovulatory infertility.
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