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The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 1 344-351
Copyright © 2004 by The Endocrine Society

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

John Somner, Susan McLellan, Joseph Cheung, Y. T. Mak, Michelle L. Frost, Karen M. Knapp, Anthony S. Wierzbicki, Michael Wheeler, Ignac Fogelman, Stuart H. Ralston and Geeta N. Hampson

Department of Chemical Pathology, St. Thomas’ Hospital (J.S., S.M., J.C., Y.T.M., A.S.W., M.W., G.N.H.), London, SE1 7EH United Kingdom; Osteoporosis Screening Unit, Guy’s Hospital (M.L.F., K.M.K., I.F.), London SE1 9RT United Kingdom; and Bone Research Group, Department of Medicine and Therapeutics, University of Aberdeen Medical School (S.H.R.), Aberdeen, AB25 2ZD United Kingdom

Address all correspondence and requests for reprints to: Geeta N. Hampson, M.D., Department of Chemical Pathology, 5th Floor, North Wing, St. Thomas’ Hospital, London, United Kingdom SE1 7 EH. E-mail: geeta.hampson{at}kcl.ac.uk.

The CYP 17 and CYP 19 genes encode 17{alpha}-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/cm2; P = 0.006). In conclusion, both CYP 17 and CYP 19 are candidate genes for osteoporosis in postmenopausal women.

Abbreviations: BMD, Bone mineral density; BMI, body mass index; CV, coefficient of variation; DHEAS, dehydroepiandrosterone sulfate; DXA, dual energy x-ray absorptiometry; LN, natural logarithm; SNP, single nucleotide polymorphism.




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