Polycystic ovary syndrome (PCOS) is a common endocrinopathy with hyperandrogenemia to be its strongest genetically determined characteristic. Our aim was to investigate the potential synergy of two functional polymorphisms: the (TAAAA)n polymorphism of the sex hormone-binding globulin gene (SHBG) known to be associated with PCOS and influence serum SHBG levels (longer repeats were associated with lower SHBG levels) and the (CAG)n polymorphism of androgen receptor gene (AR) known to affect the transcriptional activity of AR (shorter repeats were associated with higher transcriptional activity).
Subjects and methods: We studied 180 women with PCOS and 168 healthy women of reproductive age. The body mass index (BMI) was recorded and the hormonal profile was determined on 3-5th day of menstrual cycle. DNA was extracted from peripheral blood leucocytes and the SHBG(TAAAA)n and AR(CAG)n polymorphisms were genotyped. All subjects gave their consent and the local Ethical Committee approval was obtained.
Results: Genotype analysis revealed 6 SHBG(TAAAA)n alleles with 611 repeats and 19 AR(CAG)n alleles with 632 repeats. Women with PCOS had a greater frequency of longer SHBG alleles (>8 repeats) than normal women (P=0.001) while there was no difference in the distribution of AR alleles between patients and controls.
Among patients, those with both long SHBG (>8 repeats) and short AR (≤20 repeats) genotypes had the lowest SHBG levels (P=0.001) and the highest DHEAS (P=0.001), total testosterone (P=0.03), FAI (P<0.001) and 17 hydroxyprogesterone levels (P=0.03) independently of BMI.
Conclusion: Both genes affecting androgen transportation and androgen action act synergistically in PCOS phenotype. Furthermore Individuals with both the SHBG(TAAAA)n variants associated with low SHBG levels and AR(CAG)n variants associated with increased transcriptional AR gene activity are likely to be exposed to excess androgen even during fetal life and this may programme their PCOS phenotype in later life.
01 - 05 Apr 2006
European Society of Endocrinology