PRESENTATION OF NONRANDOM X CHROMOSOME INACTIVATION AND ANDROGEN RECEPTOR GENE POLYMORPHISM IN DIFFERENT PHENOTYPES OF POLYCYSTIC OVARY SYNDROME
- Authors: CHERNUKHA G.E1, NEMOVA Y.I1, BLINOVA I.V2, RUDENKO V.V3
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Affiliations:
- Academician V. I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia
- Central Clinical Hospital, Russian Academy of Sciences
- Laboratory of Epigenetics, Medical Genetics Center
- Issue: No 4 (2013)
- Pages: 38-43
- Section: Articles
- URL: https://journals.eco-vector.com/0300-9092/article/view/246932
- ID: 246932
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Abstract
Objective. To study the presentation of nonrandom X chromosome inactivation and androgen receptor (AR) gene CAG repeat polymorphism in patients with different phenotypes of polycystic ovary syndrome (PCOS). Subject and methods. The investigation enrolled 56 patients (mean age 27.3±5.74 years; body mass index (BMI) 24.2±5.47kg/m2) with PCOS and 64 healthy women (mean age 25.6±4.28 years; BMI 22.4±0.11kg/m2). The Rotterdam criteria were used to determine the reproductive phenotypes of PCOS, according to which the patients were divided into subgroups. Nonrandom X chromosome inactivation was revealed by differential methylation of active and inactive X chromosomes, followed by an analysis of CAG repeat polymorphism in the first exon of androgen receptor (AR), by applying methyl-sensitive PCR assay. Results. The rate of nonrandom X chromosome inactivation in phenotypes A and B was 61% (16/25) and 47% (8/16), respectively, which were significantly higher than the reference values 16.1% (9/56) (р<0.05). There were no differences between phenotype D [30% (3/9)] and the control group (р=0.3490). The prevalence rate of genotypes with both short alleles in the AR gene (VMTR/CAG) (n<22/<22) among the patients with phenotype D (non-androgenic) was 60% (6/10), this was 5-6 times greater than that in phenotypes A and B and among the healthy women (p<0.05). In short alleles of AR (CAG repeats < 22) and its presumptively high activity in both groups with phenotype D, the mean level of total testosterone was some 2 times lower than that in a group of patients with long alleles - phenotype A and B (1.99±0.16 pg/ml versus 3.5±0.37 and 3.32±0.19 pg/ml, respectively; р<0.05). Conclusion. The f indings suggest that there are genetic differences between the phenotypes of PCOS in the presentation rate of nonrandom X chromosome inactivation and androgen receptor gene polymorphism. In phenotype D, nonrandom X chromosome inactivation and short alleles in the AR gene were 2-fold less. This may contribute to the excess effect of androgens at their normal serum concentrations and point to the specific features of mechanisms for the formation of non-androgenic and androgenic phenotypes of PCOS.
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About the authors
G. E CHERNUKHA
Academician V. I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia
Email: c-galina1@yandex.ru
Yu. I NEMOVA
Academician V. I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia
Email: j_nemova@hotmail.com
I. V BLINOVA
Central Clinical Hospital, Russian Academy of Sciences
Email: aiblinovy@mail.ru
V. V RUDENKO
Laboratory of Epigenetics, Medical Genetics Center
Email: shkarupo@mail.ru
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