A Common Promoter Variant in the Cytochrome P450c17α (CYP17) Gene Is Associated with Bioavailable Testosterone Levels and Bone Size in Men

Authors

  • Joseph M. Zmuda,

    Corresponding author
    1. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    • Address reprint requests to: Joseph M. Zmuda, Ph.D., Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA 15261, USA
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  • Jane A. Cauley,

    1. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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  • Lewis H. Kuller,

    1. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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  • Robert E. Ferrell

    1. Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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Abstract

Cytochrome P450c17α (CYP17) encodes an enzyme with 17α-hydroxylase and 17,20-lyase activities, which is essential for the normal production of adrenal and gonadal androgens. Because androgens have powerful effects on bone growth and metabolism, we determined whether a single base pair (bp) substitution (T → C) in the promoter region (−34 bp) of CYP17 is associated with sex hormone levels, stature, and femoral mass and size in 333 white men aged 51-84 years (mean ± SD; 66 ± 7 years). Femoral neck bone mineral content (BMC), cross-sectional area (CSA), and bone mineral density (BMD) were measured using dual-energy X-ray absorptiometry (DXA). Genotype frequencies did not deviate from Hardy-Weinberg expectations. Serum bioavailable testosterone levels were 20% or 0.5 SDs higher in men with the C/C compared with the T/T genotype, whereas heterozygous men had intermediate hormone levels (p = 0.019). Men with the C/C genotype also were nearly 3 cm taller and had 0.6 SD greater femoral neck CSA than men with the T/T genotype (p ≤ 0.01 for both). The association with CSA persisted after adjusting for age, height, and body weight. In contrast, CYP17 genotype was not associated with femoral neck BMC, areal BMD (g/cm2), or estimated volumetric BMD (g/cm3). These results suggest that allelic variation at the CYP17 locus may contribute to the genetic influence on stature and femoral size in men.

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