Polymorphisms in the P450 c17 (17-Hydroxylase/17,20-Lyase) and P450 c19 (Aromatase) Genes: Association with Serum Sex Steroid Concentrations and Bone Mineral Density in Postmenopausal Women

• DOI: 10.1210/jc.2003-030164
• Publication Date: 2004-01-09T20:32:57Z
• Authors: John Somner; Susan McLellan; Joseph Cheung; Y. T. Mak; Michelle L. Frost; Karen M. Knapp; Anthony S. Wierzb...; Michael Wheeler; Ignac Fogelman; Stuart H. Ralston; Geeta N. Hampson
• Keywords: 0301 basic medicine; Polymorphism, Genetic; Estradiol; Genotype; Dehydroepiandrosterone Sulfate; Femur Neck; 610; Steroid 17-alpha-Hydroxylase; Exons; Middle Aged; Postmenopause; 03 medical and health sciences; Aromatase; Gene Frequency; Bone Density; Case-Control Studies; Linear Models; Humans; Female; Gonadal Steroid Hormones; Promoter Regions, Genetic; Osteoporosis, Postmenopausal; Aged

The CYP 17 and CYP 19 genes encode 17alpha-hydroxylase/17,20-lyase and aromatase, respectively, both involved in sex hormone synthesis. We investigated the association between 2 common polymorphisms in 1) the promoter region (T-->C substitution) of CYP 17, and 2) exon 3 (G-->A) of CYP 19, bone mineral density (BMD) and serum androgen/estradiol, in a case-control study of 252 postmenopausal women aged 64.5 +/- 9.2 yr (mean +/- SD). There was no significant difference in serum estradiol concentrations between cases (n = 136) and controls (n = 116). The CYP 19 genotype was significantly associated with serum estradiol (P = 0.002). Women with the AA genotype had higher serum estradiol concentrations compared with those with the GG genotype (P = 0.03). In older women, those with the CYP 19 GA and GG genotypes had an increased prevalence of osteoporosis (P = 0.04) and fractures (P = 0.003). We found no significant association between CYP 17 genotype and serum androgens and estradiol concentrations. However, a significant association was seen between BMD values at the femoral neck with CYP 17 genotype in cases (P = 0.04) and in the whole study population (P = 0.012). Subjects with the CC genotype had significantly lower BMD (mean +/- SD: TT, 0.7 +/- 0.16; CC, 0.6 +/- 0.08 g/cm(2); P = 0.006). In conclusion, both CYP 17 and CYP 19 are candidate genes for osteoporosis in postmenopausal women.