A common promotor variant in the cytochrome P450c17alpha (CYP17) gene is associated with bioavailability testosterone levels and bone size in men

J Bone Miner Res. 2001 May;16(5):911-7. doi: 10.1359/jbmr.2001.16.5.911.


Cytochrome P450c17alpha (CYP17) encodes an enzyme with 17a-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 < or = 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Biological Availability
  • Bone Density
  • Bone and Bones / physiopathology*
  • Cohort Studies
  • Estradiol / blood
  • Gene Frequency
  • Genetic Variation*
  • Humans
  • Male
  • Middle Aged
  • Osteoporosis / blood
  • Osteoporosis / genetics*
  • Osteoporosis / physiopathology
  • Polymorphism, Genetic
  • Promoter Regions, Genetic*
  • Steroid 17-alpha-Hydroxylase / genetics*
  • Testosterone / blood*


  • Testosterone
  • Estradiol
  • Steroid 17-alpha-Hydroxylase