Association of Polymorphisms of Interleukin-6, Osteocalcin, and Vitamin D Receptor Genes, Alone or in Combination, with Bone Mineral Density in Community-Dwelling Japanese Women and Men

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Abstract
We examined whether the −634C→G, 298C→T, and 2C→T polymorphisms of the IL-6, osteocalcin, and vitamin D receptor (VDR) genes, respectively, were associated, alone or in combination, with bone mineral density (BMD) in community-dwelling Japanese women (between 1108 and 1113) or men (between 1116 and 1130) aged 40–79 yr. The −634C→G polymorphism of the IL-6 gene and the 298C→T polymorphism of the osteocalcin gene were associated with BMD in postmenopausal women, with the respective GG and TT genotypes representing risk factors for reduced bone mass. IL-6 and osteocalcin genotypes showed additive effects on BMD for postmenopausal women. The 2C→T polymorphism of the VDR gene was associated with BMD in men, with the CT genotype contributing to reduced BMD. These results suggest that the IL-6 and osteocalcin genes are susceptibility loci for reduced BMD in postmenopausal women and that the VDR gene constitutes such a locus in men. The combined IL-6 and osteocalcin genotypes may prove informative for the assessment of osteoporosis in women.
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