Characteristics of polymorphism of genes involved in the regulation of glucose metabolism and steroid hormone synthesis in patients with polycystic ovary syndrome

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Abstract

Background: Polycystic ovary syndrome is an urgent problem of gynecological endocrinology. Currently, a number of genes have been studied that control glucose metabolism and are involved in the synthesis, conversion into an active form and transport of steroid hormones, mutations in which with a certain degree of reliability can serve as a diagnostic criterion for polycystic ovary syndrome.

Aim: The aim of this study was to evaluate the PPARG Pro12Ala, INS 223HphI A>T, and SHBG (TAAAA)n gene polymorphisms in patients with polycystic ovary syndrome and in healthy individuals.

Materials and methods: The polymerase chain reaction method and restriction fragment length polymorphism analysis were used. The frequencies of alleles and genotypes of polymorphic variants were studied in 136 women with polycystic ovary syndrome and 47 women in the control group: Pro12Ala (PPARG gene), 223HphI A>T, (INS gene) and (TAAAA)n repeats (SHBG gene).

Results: The distribution of the allele and genotype frequencies for the PPARG (rs1801282) and INS (rs689) genes in patients with polycystic ovary syndrome and in healthy individuals did not differ. The distribution of the genotype frequencies in the group of women with polycystic ovary syndrome differed (p = 0.02) from that in the control group for the (TAAAA)n polymorphism in the SHBG gene. In the presence of a long repeat in the SHBG gene in at least one of the homologous chromosomes, the probability of a woman having polycystic ovary syndrome increases by 2.5 times. Patients with a verified A/A genotype (INS), in the presence of an SHBG gene allele with a long repeat, have a ten-fold higher risk of developing polycystic ovary syndrome than women with SHBG gene short alleles.

Conclusions: Patients with long repeats in the SHBG gene are at risk for developing polycystic ovary syndrome with phenotypes A, B, and C, especially in combination with the presence of the A/A genotype, class I (INS).

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About the authors

Natalia S. Osinovskaya

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

Author for correspondence.
Email: natosinovskaya@mail.ru
ORCID iD: 0000-0001-7831-9327
SPIN-code: 3190-2307

Cand. Sci. (Biology)

Russian Federation, Saint Petersburg

Elena I. Abashova

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

Email: abashova@yandex.ru
ORCID iD: 0000-0003-2399-3108
SPIN-code: 2133-0310

MD, Cand. Sci. (Medicine)

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

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

Russian Federation, Saint Petersburg

Maria D. Bredgauer

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

Email: imd2013@yandex.ru
ORCID iD: 0009-0008-1348-029X
Russian Federation, Saint Petersburg

Iskender Yu. Sultanov

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

Email: timbuctu@mail.ru
ORCID iD: 0009-0009-5297-8848
Russian Federation, Saint Petersburg

Yulia A. Nasykhova

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

Email: yulnasa@gmail.com
ORCID iD: 0000-0002-3543-4963
SPIN-code: 9661-9416

Cand. Sci. (Biology)

Russian Federation, Saint Petersburg

Andrey S. Glotov

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

Email: anglotov@mail.ru
ORCID iD: 0000-0002-7465-4504
SPIN-code: 1406-0090

Dr. Sci. (Biology)

Russian Federation, Saint Petersburg

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Supplementary files

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2. Fig. 1. Electropherogram of PPARG Pro12Ala restriction products (bands 1–3 and 7–9: genotype Pro/Pro; bands 4–6: genotype Pro/Ala)

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3. Fig. 2. Electropherogram of INS 223HphI A>T restriction products (bands 1–3 and 5–9: genotype A/A; band 4: genotype A/T)

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4. Fig. 3. Electropherogram of SHBG (TAAAA)n amplification products (sample numbers are indicated in the upper row; the number of TAAAA repeats is shown in the lower row)

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5. Fig. 4. Distribution of phenotypes A, B, C, and D in patients with polycystic ovary syndrome (n = 123) in the presence of at least one allele with long (8 or more) TAAAA repeats in the SHBG gene promoter

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