Association of an aromatase TTTA repeat polymorphism with circulating estrogen, bone structure, and biochemistry in older women

• Published in: American journal of physiology: endocrinology and metabolism 2005-05, Vol.288 (5), p.E989-E995
• Main Authors: Dick, I. M, Devine, A, Prince, R. L
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Aging - genetics; Aging - metabolism; Aromatase - genetics; Australia - epidemiology; Bone Density - genetics; Comorbidity; Estrogens - blood; Female; Genetic Predisposition to Disease - epidemiology; Humans; Microsatellite Repeats - genetics; Middle Aged; Osteopetrosis - enzymology; Osteopetrosis - epidemiology; Polymorphism, Genetic - genetics; Risk Assessment - methods; Risk Factors; Spinal Fractures - enzymology; Spinal Fractures - epidemiology; Spinal Fractures - genetics; Statistics as Topic
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00550.2004

1 School of Medicine and Pharmacology, University of Western Australia; 2 Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital; 3 Western Australian Institute of Medical Research; and 4 School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, Western Australia Submitted 16 November 2004 ; accepted in final form 16 December 2004 Osteoporosis is a disease that is strongly genetically determined. Aromatase converts androgens to estradiol in postmenopausal women, therefore polymorphisms of the gene for this enzyme may be associated with bone mass and fracture. We investigated the association of the TTTA microsatellite polymorphism in intron 4 of the aromatase (CYP19) gene with bone mineral density (BMD) and fracture in 1,257 women aged 70 yr and greater. The data obtained were stratified based on the presence or absence of a [TTTA]n of 7 (A2), determined from a preliminary analysis of hip dual-energy X-ray absorptiometry BMD, which was present in 27% of the population. The presence of an A2 allele was associated with a higher free estradiol index (0.52 ± 0.49, P = 0.049) compared with the absence of an A2 allele (0.47 ± 0.45); higher BMD at all sites of the hip (3.4% total hip, 2.3% femoral neck, 3.6% intertrochanter, 4.1% trochanter) and the lumbar spine (12.7%); higher values for the calcaneal quantitative ultrasound parameters broadband ultrasound (1.3%), speed of sound (0.4%), and stiffness (3.7%); and higher peripheral quantitative computed tomography measures for total (3.4%), trabecular (3.3%), and cortical BMD (3.3%) and the derived stress strain index (SSI) parameters SSI polar (6.4%) and SSI x (6.8%) values. A lower deoxypryridinoline creatinine ratio was observed in subjects with an A2 allele (30.3 ± 10.4 vs. 27.1 ± 9.1, P = 0.03). The A2 allele was associated with a lower prevalence of vertebral fracture in subjects who were osteoporotic (odds ratio 0.27, confidence interval 0.09–0.79). Therefore, a common polymorphism of the aromatase gene, perhaps in linkage disequilibrium with a functionally significant CYP19 polymorphism, is associated with bone structure and bone turnover, either by local effects or by effects on circulating bioactive estrogen. estradiol; fracture; bone density Address for reprint requests and other correspondence: I. Dick, School of Medicine and Pharmacology, Univ. of Western Australia, 4th Floor G Block, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia (E