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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

Department of Gene Therapy (Y.Y.), Gifu International Institute of Biotechnology and Institute of Applied Biochemistry, Mitake, Gifu 505-0116, Japan; and Department of Epidemiology (F.A., N.N., H.S.), National Institute for Longevity Sciences, Obu, Aichi 474-8522, Japan

Address all correspondence and requests for reprints to: Yoshiji Yamada, M.D., Ph.D., Department of Gene Therapy, Gifu International Institute of Biotechnology, Yagi Memorial Park, Mitake, Gifu 505-0116, Japan. E-mail: yoyamada{at}giib.or.jp.

We examined whether the -634CG, 298CT, and 2CT 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 -634CG polymorphism of the IL-6 gene and the 298CT 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 2CT 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.

This work was supported in part by Research Grants for Longevity Sciences (12C-01) from the Ministry of Health, Labor, and Welfare of Japan (to Y.Y. and H.S.).

Abbreviations: BMD, Bone mineral density; BMI, body mass index; DXA, dual-energy X-ray absorptiometry; PCR, polymerase chain reaction; pQCT, peripheral quantitative computed tomography; RFLP, restriction fragment length polymorphism; SNP, single nucleotide polymorphism; VDR, vitamin D receptor.

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