CYP17 genotype predicts serum hormone levels among pre-menopausal women

BACKGROUND: CYP17, which encodes cytochrome P450c17α, mediates both steroid 17a-hydroxylase and 17,20-lyase activities, and is essential for the production of glucocorticoids and sex steroids. There is evidence that a common polymorphism in CYPI7 (T27C) is associated with estrogen levels, making it a potential marker of disease risk. METHODS: This is the first study to examine the relationship between CYP17 and estradiol (E 2 ) using serum sampled exclusively from the early follicular phase of the menstrual cycle. We assessed the relationship between CYP17 and serum hormone levels, menstrual cycle length, bleed length, and age at menarche in 164 pre-menopausal women. RESULTS: Among women with body mass index (BMI) ≤25 kg/m 2 , those with the TC and CC genotypes had 19 and 42% higher E 2 (P for trend 0.007) and 14 and 30% higher dehydroepiandrosterone sulphate respectively (P for trend 0.10) than women with the TT genotype. Androstenedione levels did not differ between genotypes. Among women with BMI >25 kg/m 2 , hormone levels did not differ by genotype. Women with the C allele were also more likely to have menstrual cycle lengths <27 days [odds ratio (OR) for TC = 2.36, 95% confidence interval (CI) = 1.24-4.52; OR for CC = 5.59, 95% CI = 1.53-20.43 compared to TT]. CYPI7 genotype was not associated with menstrual bleed length or age at menarche. CONCLUSION: The CYPI7 T27C polymorphism may be a marker of endocrine function.