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Hum. Reprod. Advance Access published online on May 5, 2005
Human Reproduction, doi:10.1093/humrep/dei054
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received January 25, 2005
Revised April 4, 2005
Accepted April 7, 2005

Article

CYP17 genotype predicts serum hormone levels among pre-menopausal women

Chanley M. Small 1*, Michele Marcus 1, Stephanie L. Sherman 2, Amy K. Sullivan 2, Amita K. Manatunga 3, and Heather Spencer Feigelson 4

1 Department of Epidemiology,, USA
2 Department of Human Genetics and, USA
3 Department of Biostatistics, Emory University, Atlanta, Georgia and
4 American Cancer Society, Atlanta, Georgia, USA

* To whom correspondence should be addressed.
Chanley M. Small, E-mail: csmall{at}sph.emory.edu


  Abstract

BACKGROUND: CYP17, which encodes cytochrome P450c17{alpha}, mediates both steroid 17{alpha}-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 CYP17 (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 (E2) 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/m2, those with the TC and CC genotypes had 19 and 42% higher E2 (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/m2, 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]. CYP17 genotype was not associated with menstrual bleed length or age at menarche. CONCLUSION: The CYP17 T27C polymorphism may be a marker of endocrine function.

Keywords: CYP17/estradiol/menstrual cycle/P450(c17)/sex hormones.
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