The Human Calcium-Sensing Receptor and Interleukin-6 Genes are Associated with Bone Mineral Density in Chinese

Calcium sensing receptor (CASR) is a central factor involved in calcium metabolism. Interleukin-6 (IL-6) is a pleiotropic cytokine that plays an important role in osteoclast differentiation. Thus, both CASR and IL-6 are important in bone and mineral metabolism and are prominent candidate genes for osteoporosis. The study aimed to test association and/or linkage between the CASR and IL-6 genes with bone mineral density (BMD) variation in a Chinese population. A cytosine-adenine (CA)_n repeat polymorphism in the CASR gene and the IL-6 gene was genotyped, respectively, in 1 263 subjects from 402 Chinese nuclear families. Employing tests implemented in the program QTDT (quantitative transmission disequilibrium tests), a significant total association of the CASR (CA)₁₂ allele (P = 0.006) and (CA)₁₈ allele (P = 0.02) with BMD at the femoral neck was found. For the IL-6 gene, significant within-family associations were found between the (CA)₁₄ allele and BMD at the total hip (P = 0.021), the femoral neck (P = 0.041), and the intertrochanteric region (P = 0.029). A significant linkage was also observed between IL-6 CA repeat polymorphism and BMD at the spine (P = 0.001). The results suggest that the CASR gene and the IL-6 gene may have effects on BMD variation in Chinese.