ROLE OF GENETIC AND AUTOIMMUNE DISORDERS IN THE DEVELOPMENT OF PREMATURE OVARIAN FAILURE

Objective. To reveal an association of CGG repeat lengths in the FMR1 gene with the genesis of premature ovarian failure (POF). Subjects and methods. The study enrolled 78 patients with POF who underwent molecular genetic testing and autoimmune screening. The patients were divided into 3 groups: A) carriers of less than 26 repeats; B) women in whom both alleles had a normal range of repeats (26-34); C) those who had more than 34 CGG repeats. The genesis of the disease was determined in all three groups. Results. A comparative intergroup analysis indicated that the autoimmune genesis of POF was statistically significantly more common in the women with normal lengths of CGG repeats than in the carriers of a larger or smaller number of CGG repeats (71.8, 8.32, and 4.54% in Groups В, A, and С, respectively; р=0.002). Among the patients with the autoimmune genesis of POF, the proportion of patients with a normal CGG repeat length was 88.4%. A comparative analysis of hormonal parameters ascertained that in 26 patients with the autoimmune genesis of POF, the level of anti-Müllerian hormone averaged 0.13±0.03 ng/ml versus 0.06±0.01 ng/ml (p<0.05) in the patients with other causes of the disease, which is indicative of some preservation of a primordial pool in autoimmune lesions. Conclusion. The normal length of CGG repeats in the FMR1 gene in patients with POF may be suggestive of its autoimmune form as autoimmune determinants rather than molecular genetic causes are to a greater extent involved in its development. At the same time the abnormal length of CGG repeats may be an early predictor of the development of the molecular genetic form of POF.

fragile X mental retardation 1 (FMR1) gene, premature ovarian failure, anti-Müllerian hormone, anti-ovarian antibodies