title: A common promotor variant in the cytochrome P450c17alpha (CYP17) gene is associated with bioavailability testosterone levels and bone size in men.
abstract: 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.
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pennsylvania 15261, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Zmuda
authors.forename: J A
authors.initials: JA
authors.lastname: Cauley
authors.forename: L H
authors.initials: LH
authors.lastname: Kuller
authors.forename: R E
authors.initials: RE
authors.lastname: Ferrell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001682:Biological Availability; D015519:Bone Density; D001842:Bone and Bones / Q000503:physiopathology*; D015331:Cohort Studies; D004958:Estradiol / Q000097:blood; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*; D013739:Testosterone / Q000097:blood*
chemical_list: D013739:Testosterone; D004958:Estradiol; D013254:Steroid 17-alpha-Hydroxylase