ROLE OF NONRANDOM X-CHROMOSOME INACTIVATION AND ANDROGEN RECEPTOR POLYMORPHISM IN POLYCYSTIC OVARY SYNDROME
- Authors: CHERNUKHA G.E1, BLINOVA I.V2, NEMOVA Y.I1, RUDENKO V.V3
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Affiliations:
- Academician V. I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia
- Central Clinical Hospital, Russian Academy of Sciences, Moscow
- Medical Genetics Center, Russian Academy of Medical Sciences, Moscow
- Issue: No 6 (2012)
- Pages: 33-39
- Section: Articles
- URL: https://journals.eco-vector.com/0300-9092/article/view/246789
- ID: 246789
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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 polycystic ovary syndrome (POS). Subjects and methods. The study enrolled 53 patients with POS and 64 healthy women with regular menstrual cycles. Nonrandom X-chromosome inactivation was detected by differential methylation of active and inactive X chromosome, followed by AR gene exon 1 CAG repeat polymorphism analysis, by applying the methyl-sensitive polymerase chain reaction. Results. In the POS group, nonrandom X-chromosome inactivation was found in 54% (27/50) of cases, which was 3.4 times as often as that in the control group — 16.1% (9/56) (p<0.0001). A study of AR CAG repeat lengths indicated that the alleles with a repeat length of 23 (CAG) and 19 (CAG) were most common in 13% (14/106) and 18.8% (24/128) in the POS and control groups, respectively. The mean sum of the two alleles (SBM) did not differ between the groups and were 22.02±2.77 and 21.42±2.26, respectively (р>0.05). There was a relationship of the clinical manifestations of POS to the genotype of the patients: more severe impairments in the menstrual cycle were observed in the patients with random X-chromosome inactivation. This group of patients showed a relationship of AR gene CAG repeat lengths to the level of androgens. In the patients with long repeat length alleles for AR (GAC repeats ≥22) and its low activity, the mean level of free testosterone was 3 times as high as that in those with short repeat length alleles (7.49±5.79 versus 2.27±1.81pg/ml; р=0.0017). Conclusion. Every two patients with POS were found to have nonrandom X-chromosome inactivation associated with more pronounced ovarian dysfunction. There were no differences in AR CAG repeat lengths between the control and POS groups; however, the nonrandom X-chromosome inactivation group displayed a relationship of long repeat length alleles to the high levels of free testosterone. This may be considered as one of the mechanisms for the development of hyperandrogenism in POS.
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About the authors
G. E CHERNUKHA
Academician V. I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia
Email: c-galinal@yandex.ru
I. V BLINOVA
Central Clinical Hospital, Russian Academy of Sciences, Moscow
Email: aiblinovy@mail.ru
Yu. I NEMOVA
Academician V. I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia
Email: j_nemova@hotmail.com
V. V RUDENKO
Medical Genetics Center, Russian Academy of Medical Sciences, Moscow
Email: shkarupo@mail.ru
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