Genetic markers, bone mineral density, and serum osteocalcin levels

We evaluated five genetic markers for products that contribute to skeletal mineralization including the Spl polymorphism for type I collagen Ai (COLIA 1), the vitamin D receptor (VDR) translation initiation site polymorphism, the promoter of the osteocalcin gene containing a C/T polymorphism, the est rogen receptor (ER) gene containing a TA repeat, and the polymorphic (AGC)( n) site in the androgen receptor. These markers were evaluated for their po tential relationship with bone mineral density (BMD), measured by dual-ener gy X-ray densitometry, or its 3-year change. Additionally, potential associ ations of these genotypes and with baseline osteocalcin concentration or it s 3-year change (assessed using radioimmunoassay) were evaluated. The study was conducted in 261 pre- and perimenopausal women of the Michigan Bone He alth Study, a population-based longitudinal study of musculoskeletal charac teristics and diseases. The polymorphic (AGC)(n) site in the androgen recep tor showed a strong association with BMD of the femoral neck; (FN) and lumb ar spine and remained highly significant after adjusting for body mass inde x (BMI), oophorectomy/hysterectomy, oral contraceptive (OC) use and hormone replacement use (p < 0.001), The TA repeat at the 5' end of the ER gene wa s associated with total body calcium (p < 0.05) after adjusting for BMI, oo phorectomy and hysterectomy, and OC use. The frequency of oophorectomy and hysterectomy within selected genotypes explained much of the statistically significant association of the ER genotypes with BMD of the FN and spine, T here was no association of measures of BMD or bone turnover with the Spl po lymorphism for COLIA1, the VDR translation initiation site polymorphism, or the C/T promoter polymorphism of the osteocalcin gene. These findings sugg est that sex hormone genes may be important contributors to the variation i n BMD among pre- and perimenopausal women.