caa a22 4500 605463026 CHVBK 20210128100251.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s00774-014-0636-0 doi (NATIONALLICENCE)springer-10.1007/s00774-014-0636-0 A missense single nucleotide polymorphism, V114I of the Werner syndrome gene, is associated with risk of osteoporosis and femoral fracture in the Japanese population [Elektronische Daten] [Heying Zhou, Seijiro Mori, Masashi Tanaka, Motoji Sawabe, Tomio Arai, Masaaki Muramatsu, Makiko Mieno, Shoji Shinkai, Yoshiji Yamada, Motohiko Miyachi, Haruka Murakami, Kiyoshi Sanada, Hideki Ito] Werner syndrome is a rare autosomal recessive disorder caused by mutations in the human WRN gene and characterized by the early onset of normal aging symptoms. Given that patients with this disease exhibit osteoporosis, the present study aimed to determine whether the WRN gene contributes to the etiology of osteoporosis. A genetic association study of eight non-synonymous polymorphisms in the WRN gene and the incidence of femoral fracture was undertaken in 1,632 consecutive Japanese autopsies in which 140 patients had experienced the fracture during their lifetime. The results were validated in 251 unrelated postmenopausal Japanese women with osteoporosis and 269 non-institutionalized, community-dwelling Japanese adults. A statistically significant association was observed between rs2230009 (c.340G>A)—which results in a Val to Ile substitution—and fracture risk; the incidence of femoral fracture increased dose-dependently with the number of A alleles (p=0.0120). Femoral neck bone and whole bone densities were lower among postmenopausal women with osteoporosis and community-dwelling adults, respectively, if they were of the AG instead of the GG genotype. The results suggest that Japanese subjects bearing at least one A allele of rs2230009 of the WRN gene are at a significantly higher risk of femoral fracture, possibly due to decreased bone density. The Japanese Society for Bone and Mineral Research and Springer Japan, 2015 Femoral fracture nationallicence Osteoporosis nationallicence Single nucleotide polymorphism nationallicence Werner syndrome nationallicence Zhou Heying Center for Promotion of Clinical Investigation, Tokyo Metropolitan Geriatric Hospital, 35-2 Sakae, 173-0015, Itabashi, Tokyo, Japan aut Mori Seijiro Center for Promotion of Clinical Investigation, Tokyo Metropolitan Geriatric Hospital, 35-2 Sakae, 173-0015, Itabashi, Tokyo, Japan aut Tanaka Masashi Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan aut Sawabe Motoji Section of Molecular Pathology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan aut Arai Tomio Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan aut Muramatsu Masaaki Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan aut Mieno Makiko Department of Medical Informatics, Center for Information, Jichi Medical University, Shimotsuke, Tochigi, Japan aut Shinkai Shoji Research Team for Social Participation and Community Health, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan aut Yamada Yoshiji Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie, Japan aut Miyachi Motohiko Department of Health Promotion and Exercise, National Institute of Health and Nutrition, Tokyo, Japan aut Murakami Haruka Department of Health Promotion and Exercise, National Institute of Health and Nutrition, Tokyo, Japan aut Sanada Kiyoshi Faculty of Sport and Health Science, Ritsumeikan University, Kita, Shiga, Japan aut Ito Hideki President, Local Independent Administrative Agency, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan aut Journal of Bone and Mineral Metabolism Springer Japan 33/6(2015-11-01), 694-700 0914-8779 33:6<694 2015 33 774 https://doi.org/10.1007/s00774-014-0636-0 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00774-014-0636-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhou Heying Center for Promotion of Clinical Investigation, Tokyo Metropolitan Geriatric Hospital, 35-2 Sakae, 173-0015, Itabashi, Tokyo, Japan aut NATIONALLICENCE 700 1- Mori Seijiro Center for Promotion of Clinical Investigation, Tokyo Metropolitan Geriatric Hospital, 35-2 Sakae, 173-0015, Itabashi, Tokyo, Japan aut NATIONALLICENCE 700 1- Tanaka Masashi Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan aut NATIONALLICENCE 700 1- Sawabe Motoji Section of Molecular Pathology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan aut NATIONALLICENCE 700 1- Arai Tomio Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan aut NATIONALLICENCE 700 1- Muramatsu Masaaki Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan aut NATIONALLICENCE 700 1- Mieno Makiko Department of Medical Informatics, Center for Information, Jichi Medical University, Shimotsuke, Tochigi, Japan aut NATIONALLICENCE 700 1- Shinkai Shoji Research Team for Social Participation and Community Health, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan aut NATIONALLICENCE 700 1- Yamada Yoshiji Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie, Japan aut NATIONALLICENCE 700 1- Miyachi Motohiko Department of Health Promotion and Exercise, National Institute of Health and Nutrition, Tokyo, Japan aut NATIONALLICENCE 700 1- Murakami Haruka Department of Health Promotion and Exercise, National Institute of Health and Nutrition, Tokyo, Japan aut NATIONALLICENCE 700 1- Sanada Kiyoshi Faculty of Sport and Health Science, Ritsumeikan University, Kita, Shiga, Japan aut NATIONALLICENCE 700 1- Ito Hideki President, Local Independent Administrative Agency, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan aut NATIONALLICENCE 773 0- Journal of Bone and Mineral Metabolism Springer Japan 33/6(2015-11-01), 694-700 0914-8779 33:6<694 2015 33 774