The human
androgen receptor (AR) gene contains a variable number of CAG repeats within exon 1. Shorter AR alleles, by increasing transactivation, may result in augmented AR-mediated sensitivity of the hair follicle. We have evaluated whether the number of CAG repeats, or if skewed inactivation of X-chromosome, favoring the presence of shorter AR alleles, influence
hirsutism in women with and without hyperandrogenemia. Twenty-eight women with idiopathic
hirsutism (normal serum
androgens), 34 women with hyperandrogenic
hirsutism (increased serum
androgens), and 15 healthy control women were analyzed by evaluating the number of CAG repeats in genomic
DNA, as well as the methylation pattern (after
DNA digestion with HpaII), which allows identification of which allele is inactive. Despite marked differences among the groups in serum
androgens, which were markedly increased in women with hyperandrogenic
hirsutism as compared with women with idiopathic
hirsutism and to controls, there were no significant differences among the groups in the number of CAG repeats. Moreover, skewed X-chromosome inactivation was found in 10 subjects (3 with idiopathic
hirsutism, 5 with hyperandrogenic
hirsutism, and 2 controls; P = 0.746) of the 67 women (14.9%) who were heterozygous for the AR gene. In several of these subjects, it was the shorter allele that was preferentially inactivated. In conclusion, neither the CAG repeat polymorphism in the AR gene, nor skewed X-chromosome inactivation, seem to play a significant role in the pathogenesis of
hirsutism.