Association of CTR and COLIA1 alleles with BMD values in peri- and postmenopausal women

The variability of bone mass and bone strength is in part genetically deter mined. The pathophysiology of the disease is complex and its heritability i s almost certainly polygenic. In a large group of women from north eastern Italy, homogeneous for calcium intake and other risk factors for osteoporos is, we investigated three different genetic polymorphic markers that have b een associated with bone mineral density (BMD). The study includes 663 post menopausal (aged 48-85 years) and 52 perimenopausal (aged 47-53 years) wome n. Lumbar spine and hip BMD were measured by dual energy X-ray absorptiomet ry (DXA). After DNA extraction, the restriction enzymes utilized were MscI for the SP1 site of the collagen type I regulatory region (COLIA1), AluI fo r the calcitonin receptor (CTR) gene, and BsmI for the Vitamin D receptor ( VDR) gene. COLIA1 genotype was significantly associated with age-adjusted h ip BMD, with the highest values in the SS group and the lowest in the ss gr oup (p < 0.05). The COLIA1 effect was not visible until the sixth decade of life, but it increased thereafter with aging, becoming statistically signi ficant also at the lumbar spine in subjects aged >70 years. CTR genotype wa s also significantly related to bone mass in the CC group, with the lowest age and weight-adjusted BMD values at the spine (p < 0.05). The CTR genotyp e effect was greater in the younger subset of women. This suggests that the CTR genotype might influence the process of acquiring peak bone mass rathe r than the process of bone loss along aging. No trend association was found between BMD values and VDR genotype. These findings suggest an association between the COLIA1 gene polymorphism more with the age-related rate of bon e loss than with peak bone mass, which apparently is somewhat affected by C TR gene polymorphism.