The role of polymorphic variants of the kisspeptin gene in the pathogenesis of ovarian insufficiency in patients with type 1 diabetes mellitus, genital endometriosis and combination of these diseases

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Abstract

BACKGROUND: Type 1 diabetes mellitus and genital endometriosis have a negative impact on female reproductive system. There is an opinion that kisspeptin plays an important role in the pathogenesis of ovarian insufficiency in patients with diabetes and endometriosis.

AIM: The aim of this study was to evaluate the role of the kisspeptin gene (KISS1) polymorphism in the pathogenesis of ovarian insufficiency in patients with type 1 diabetes mellitus, genital endometriosis and in women with combination of these diseases.

MATERIALS AND METHODS: The allele and genotype frequencies of the polymorphic variants rs5780218 (c.–145delT) and rs3924587 (c.–89G>A) of the KISS1 gene were evaluated in 258 women using polymerase chain reaction-restriction fragment length polymorphism technique. This study included 73 patients with type 1 diabetes mellitus, 83 patients with genital endometriosis, 35 patients with combination of type 1 diabetes mellitus and genital endometriosis, and 67 control subjects. The control group is represented by women of the population.

RESULTS: The analysis of the KISS1 gene showed that incidence rates of type 1 diabetes mellitus, genital endometriosis and combination of these diseases do not differ in the presence of the ins/del, del/del, and ins/ins (rs5780218) genotypes. Thus, the del allele and the ins/del and del/del genotypes are not associated with an increased risk of these diseases. It was found that in patients with type 1 diabetes mellitus, the frequency of normogonadotropic ovarian insufficiency was higher (odds ratio 15.955; 95% confidence interval 4,47–57,0; p < 0.05) in the presence of the G/A genotype according to the polymorphic variant rs3924587 compared to the G/G genotype.

CONCLUSIONS: The data obtained allow for explaining the high incidence of ovarian insufficiency in women with type 1 diabetes mellitus. In patients with type 1 diabetes mellitus with the G/A genotype who are planning pregnancy, even in case of regular menstrual cycle, it is advisable to perform hormone blood tests in dynamics for timely diagnosis of ovarian insufficiency and prescription of hormonal therapy.

About the authors

Elena V. Misharina

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Author for correspondence.
Email: mishellena@gmail.com
ORCID iD: 0000-0002-0276-7112
SPIN-code: 7350-5674
Scopus Author ID: 57200069538
ResearcherId: K-2720-2018

MD, Cand. Sci. (Med.)

Russian Federation, Saint Petersburg

Natalia S. Osinovskaya

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: natosinovskaya@mail.ru
ORCID iD: 0000-0001-7831-9327
SPIN-code: 3190-2307
Scopus Author ID: 6507794800
ResearcherId: K-1168-2018

Cand. Sci. (Biol.)

Russian Federation, Saint Petersburg

Maria I. Yarmolinskaya

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: m.yarmolinskaya@gmail.com
ORCID iD: 0000-0002-6551-4147
SPIN-code: 3686-3605
Scopus Author ID: 7801562649
ResearcherId: P-2183-2014

MD, Dr. Sci. (Med.), Professor of the Russian Academy of Sciences

Russian Federation, Saint Petersburg

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Supplementary files

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2. Fig. 1. Relations to the Hardy-Weinberg equilibrium according to the polymorphic variant rs5780218 (c.-45delT) of the KISS1 gene in the study groups. DM — diabetes mellitus; GE — genital endometriosis

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3. Fig. 2. Distribution of allele and genotype frequencies of the polymorphic variant rs5780218 (c.–45delT) of the KISS1 gene in the study groups. DM — diabetes mellitus; GE — genital endometriosis

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4. Fig. 3. Distribution of allele and genotype frequencies of the polymorphic variant rs3924587 (c.–89G>A) of the KISS1 gene in the study groups. DM — diabetes mellitus; GE — genital endometriosis

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5. Fig. 4. The frequency of normogonadotropic ovarian insufficiency depending on the genotype according to the rs3924587 variant of the KISS1 gene in women with type 1 diabetes mellitus (odds ratio 15,955)

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