FMR1 GENE POLYMORPHISM IN POLYCYSTIC OVARY SYNDROME

Objective. To study the frequency of different alleles of highly polymorphic CGG repeat in the FMR1 gene in patients with polycystic ovary syndrome (POS) and their relationship to the functional state of the reproductive system. Subjects and methods. The CGG-repeat alleles in the FMR1 gene were determined in 115patients with POS, by using a methylation-specific polymerase chain reaction (MS-PCR) assay, followed by a fragment analysis of the products conjugated with the fluorescence dye FAM. Results. The range (according to the results of previous investigations) of 28-36 CGG trinucleotide repeats in the FMR1 gene was taken as a conventional normal value in reference to the ovarian reserve in a Russian population. With this in mind, the investigators identified 3 groups of patients: who had a short (<28) allele a, who had a normal (28-36) allele b and who had a long (>36) allele c. There were 5 subgenotypes: aa in 7% of the patients; ab in 22.8%; bb in 50.9%; be in 14.9%; and ac in 4.4%>. The length of CGGrepeats in the FMR1 gene were in the reference values (bb) in 50.9% of the patients with POS; accordingly 49.1% had abnormal alleles (a and c). In accordance with the subgenotypes, there were 3 study groups: 1) 58 (50.9%) patients (bb); 2) 43 (37.7%) patients with one abnormal (short or long) allele (be, ab), and 3) 13 (11.4%) with two abnormal alleles (ac, aa). There was a two-fold increase in the incidence of amenorrhea in patients in Group 3 as compared to those in Groups 1 and (29% versus 13 and 15%, respectively; p<0.05). The mean level of anti-Mullerian hormone increased with abnormal alleles; in Group 3, it was significantly higher than in Groups 1 and 2(17.8+5.4pg/ml versus 12.1±2.6and 14.3±9.8pg/ml, respectively; p < 0.05). Longer CGG repeats were detectable in patients with infertility versus those with preserved fertility (32±4.08 versus 20.5±1.71 (1-CGG) and 33±5.04 versus 24±3.57(2-CGG) (p < 0.001). Conclusion. Regardless of the phenotype of POS, every two patients with this condition are found to have the abnormal number of CGG repeats in the FMR1 gene, which is associated with severer ovulatory dysfunction. The high rate of the presentation of abnormal alleles in the FMR1 gene, which is comparable with that in POS, may suggest that there is a similarity of molecular genetic changes in the pathogenesis of impaired folliculogenesis in these conditions.

gene polymorphic variants, CGG repeats, FMR1 gene, polycystic ovary syndrome