title: A missense single nucleotide polymorphism, V114I of the Werner syndrome gene, is associated with risk of osteoporosis and femoral fracture in the Japanese population.
abstract: 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.
authors: Center for Promotion of Clinical Investigation, Tokyo Metropolitan Geriatric Hospital, 35-2 Sakae, Itabashi, Tokyo, 173-0015, Japan.
authors: Heying
authors: H
authors: Zhou
authors: Center for Promotion of Clinical Investigation, Tokyo Metropolitan Geriatric Hospital, 35-2 Sakae, Itabashi, Tokyo, 173-0015, Japan. mori_seijiro@tmghig.jp.
authors: Seijiro
authors: S
authors: Mori
authors: Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors: Masashi
authors: M
authors: Tanaka
authors: Section of Molecular Pathology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Motoji
authors: M
authors: Sawabe
authors: Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.
authors: Tomio
authors: T
authors: Arai
authors: Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Masaaki
authors: M
authors: Muramatsu
authors: Department of Medical Informatics, Center for Information, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors: Makiko Naka
authors: MN
authors: Mieno
authors: Research Team for Social Participation and Community Health, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors: Shoji
authors: S
authors: Shinkai
authors: Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie, Japan.
authors: Yoshiji
authors: Y
authors: Yamada
authors: Department of Health Promotion and Exercise, National Institute of Health and Nutrition, Tokyo, Japan.
authors: Motohiko
authors: M
authors: Miyachi
authors: Department of Health Promotion and Exercise, National Institute of Health and Nutrition, Tokyo, Japan.
authors: Haruka
authors: H
authors: Murakami
authors: Faculty of Sport and Health Science, Ritsumeikan University, Kita, Shiga, Japan.
authors: Kiyoshi
authors: K
authors: Sanada
authors: President, Local Independent Administrative Agency, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan.
authors: Hideki
authors: H
authors: Ito
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D001344:Autopsy; D001823:Body Composition; D005090:Exodeoxyribonucleases / Q000235:genetics*; D005260:Female; D005264:Femoral Fractures / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D010024:Osteoporosis / Q000150:complications / Q000235:genetics*; D015663:Osteoporosis, Postmenopausal / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D053484:RecQ Helicases / Q000235:genetics*; D012307:Risk Factors; D000071657:Werner Syndrome Helicase
chemical_list: D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase
keywords: Femoral fracture; Osteoporosis; Single nucleotide polymorphism; Werner syndrome
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