CAG repeat polymorphism in women with PCOS and healthy controls
Ralitsa Robeva, Desislava Dobreva, Georgi Kirilov, Tcvetosar Mechandjiev, Analia Tomova, Aleksey Savov & Filip Kumanov
The androgen receptor (AR) polymorphism is determined by a variable number of CAG triplets in exon 1 of the AR gene, located on the X chromosome. CAG polymorphism could modulate different hyper- or hypoandrogenic conditions, but its influence on the polycystic ovarian syndrome (PCOS) in different ethnic populations is controversial. Therefore, we investigated the influence of the AR polymorphism on the hormonal factors and clinical signs in 52 women with PCOS and in 41 non-hirsute healthy controls from Caucasian population. The short allele, the long allele and the mean biallelic number were determined in each person. The anthropometric values, modified Ferriman-Gallwey score, and the levels of testosterone, SHBG, free testosterone, LH, FSH, estradiol and insulin were examined.
Mean numbers of CAG repeats in the long allele and the short allele as well as the mean biallelic number did not differ between the patients and controls (P>0.05). In the group of PCOS women, those with longer CAG mean biallelic number had higher LH/testosterone ratio (P=0.026). Patients with higher CAG number in the long allele had higher LH levels (P=0.046) and tendency to higher LH/testosterone ratio (P=0.064) and SHBG levels (P=0.068). The women with mean biallelic number in the lower tertile had higher Ferriman-Gallwey score in comparison to those in the intermediate tertile (P=0.037) as well as lower SHBG levels (P=0.042) despite the similar concentrations of the free and total testosterone.
In conclusion, CAG repeat polymorphism is not crucial for the development of the PCOS. However, patients with lowest number of CAG repeats have most pronounced hirsutism; while longer allele carriers have higher LH levels and LH/testosterone ratio. Consequently, CAG polymorphism of the androgen receptor could modulate the PCOS phenotype through its influence on different levels (pituitary, liver, pilosebaceous unit).
Supported by: National Science Fund, MOMN, L-1504/2005.