Polymorphic (CAG)n repeats in the androgen receptor gene: a risk marker for endometriosis and uterine leiomyomas

Endometriosis and uterine leiomyomas are leading hormone responsive, benign uterine disorders responsible for high morbidity in women of reproductive age group. A polymorphic (CAG)n repeat length located in exon 1 of the androgen receptor (AR) gene has been proposed as a risk marker for both endometriosis and leiomyomas in some ethnic groups. The present study was carried out to assess the frequency of AR (CAG)n repeat polymorphism as a risk marker for endometriosis and uterine leiomyomas in Asian Indian women.

DNA was isolated from peripheral blood samples of 331 subjects, which include 90 endometriosis cases, 140 cases of leiomyomas and 101 healthy age- and sex-matched controls. PCR was carried out to amplify exon 1 of the AR gene. All the PCR amplicons were analysed initially on 2% agarose gel electrophoresis, followed by bidirectional sequencing to calculate the number CAG repeats in individuals.

The CAG repeat ranges detected in endometriosis cases were 4-33 (Mode-19) and in leiomyomas cases 5-34 (Mode-20), whereas in controls it was 5-34 (Mode-22). A distinct variation was observed in the three groups at 14, 18, 19, 20 and 22 (CAG)n repeats, which were statistically analyzed using chi-square and odds ratio tests. 19 CAG repeats were found to be higher in endometriosis cases (19.09%) when compared with controls (9.04%), while 20 CAG repeats were higher in leiomyomas cases (14.02%) compared to controls (6.14%). A statistically significant (P < 0.05) association was observed in 19 and 20 CAG repeats in endometriosis and leiomyomas, respectively.

This is the first report from an Asian Indian population proposing that 19 and 20 CAG repeats of the AR gene are associated with endometriosis and leiomyoma and can be regarded as high-risk markers.