Association of amino acid variation (Trp64Arg) in the beta3-adrenergic receptor gene with bone mineral density |
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Authors: | Sumito Ogawa Mitsuru Emi Masataka Shiraki Takayuki Hosoi Hajime Orimo Yasuyoshi Ouchi Satoshi Inoue |
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Institution: | Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo,;Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kawasaki,;Research Institute and Practice for Involutional Diseases, Nagano,;Tokyo Metropolitan Geriatric Hospital, Tokyo,;Research Center for Genomic Medicine, Saitama Medical School, Saitama, and;CREST, Japan Science and Technology Corporation, Saitama, Japan |
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Abstract: | Background: Recent studies have revealed that a mis-sense mutation replacing tryptophan with arginine at codon 64 (Trp64Arg) of the beta3-adrenergic receptor ( β3-AR ) gene was associated with insulin resistance in non-diabetic subjects and to earlier onset of non-insulin dependent diabetes mellitus. To analyze a possible involvement of β3-AR in bone metabolism, we investigated the association between bone mineral density (BMD) and the Trp64Arg polymorphism. Methods: A large cohort of Japanese postmenopausal women comprised the study population. The genotypic frequencies in this cohort were Trp/Trp, 61.8%; Trp/Arg, 33.2%; and Arg/Arg, 5.0%. Results: When the subjects were separated into two groups, one bearing at least one Trp allele at codon 64 (Trp/Trp and Trp/Arg) and the other with none (Arg/Arg), the former subjects had significantly higher Z scores for total-body BMD (mean ± SD, 0.432 ± 0.93 versus ?0.135 ± 0.93; P = 0.033). Conclusions: These data suggested an association between this single-nucleotide polymorphism (SNP) in the β3-AR gene and BMD, and therefore a possible involvement of the Arg allele (or the absence of Trp64) in postmenopausal osteoporosis among Japanese women. |
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Keywords: | beta3-adrenergic receptor genetics osteoporosis polymorphism |
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