Longer CAG repeat length in the androgen receptor gene is associated with premature ovarian failure

Premature ovarian failure (POF) is a disorder characterized by lack of ovulation and elevated serum gonadotrophin levels before the age of 40 years. The cause of POF in most cases is unknown. As mice lacking the Androgen receptor (Ar) gene reportedly have a POF-like phenotype, we hypothesize that, variations in the AR gene maybe one of the causative factors for POF in humans. Thus the objective of the study is to evaluate the number of CAG repeats in exon 1 of the AR gene in non-familial, non-syndromic cases of POF.

A clinic-based case-control study. Seventy-eight patients with non-familial, non-syndromic POF, and 90 controls were recruited to investigate the CAG repeat numbers in exon 1 of the AR gene by PCR and Gene Scan analysis.

The mean CAG repeat length in exon 1 of the AR gene of women with POF was 23.6 +/- 3.8, which was significantly higher than controls (20.08 +/- 3.45) (P < 0.001). The biallelic mean CAG repeat ranged from 11 to 32 in the control women, compared to 16 to 30 in the POF patients. The 22 CAG repeat allele followed by the 24 CAG repeat allele was found to be at highest frequency (15.38 and 12.8%) in POF cases, although the 19 CAG repeat allele was observed at highest frequency (12.2%) in controls.

The observation suggests that the CAG repeat length is increased in women with POF as compared with controls, and may be pathogenic for POF, at least in a subset of Indian women.