THE FMR1 GENE: NEW POSSIBILITIES OF ASSESSING THE OVARIAN RESERVE

Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia, Moscow Objective. To reveal the ranging number of CGG repeats in patients with premature ovarian failure (POF) and their associations with the level of anti-Müllerian hormone (AMH). Subjects and methods. At the first stage of the study, the patients were divided into 3 groups (A, B, and C) according to the number of CGG repeats in the alleles (allele 1 with a smaller number of repeats and 2 with their larger number). At the second stage, these were classified into 3 groups according to the found zygosity in the fragile X mental retardation (FMR1) gene. Group 1 included women with both alleles being in the normal range of repeats, i.e. 26-34 repeats; Group 2 comprised the heterozygous carriers of the abnormal number of repeats, i.e. one allele was in the normal range, the other was outside this range; Group 3 consisted of women having the alleles outside the normal range of CGG repeats (26>CGG>34). A statistical correlation was determined between the number of repeats and the parameters of the ovarian reserve. Results. In the patients with POF, the frequency of both normal and abnormal lengths of CGG repeats in the FMR1 gene was practically equal (45 versus 55%). The group with the normal number of repeats (Group B) showed a statistically significant increase in the level of AMH as compared to the short (Group A) and long (Group C) number of repeats (0.49±1.13, 0.1±0.14, and 0.09±0.15 pg/ml, respectively; p < 0.05). The patients with a drastically diminished ovarian reserve were more typified by shorter CGG repeat lengths than their extension (34 versus 11%), which was slightly different from the conventional viewpoint given in the literature. Most authors previously pointed out that longer CGG repeat lengths in the grey (41-50) and permutation (51-200) zones were of diagnostic value. Comparative analysis revealed a direct moderate correlation between the number of CGG repeats in the FMR1 gene and the level of AMH in Group A (r = 0.358; p < 0.05). At the same time, Group C exhibited an inverse moderate correlation between the number of repeats and the concentration of AMH (r = -0.3174; p < 0.05). No correlation was found between the level of AMH and age in the group with the normal number of repeats. The content of AMH was moderately inversely proportional to age in the groups with the homozygous and heterozygous carriage of abnormal CGG repeat lengths. Conclusion. The length of CGG repeats in the FMR1 gene may be certainly one of the early objective predictors of POF and serve as a new test for the prediction of ovarian functional activity.

fragile X mental retardation (FMR1) gene, premature ovarian failure, anti-Müllerian hormone