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

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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.