Zhou Heying, Mori Seijiro, Tanaka Masashi, Sawabe Motoji, Arai Tomio, Muramatsu Masaaki, Mieno Makiko Naka, Shinkai Shoji, Yamada Yoshiji, Miyachi Motohiko, Murakami Haruka, Sanada Kiyoshi, Ito Hideki
Center for Promotion of Clinical Investigation, Tokyo Metropolitan Geriatric Hospital, 35-2 Sakae, Itabashi, Tokyo, 173-0015, Japan.
Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
J Bone Miner Metab. 2015 Nov;33(6):694-700. doi: 10.1007/s00774-014-0636-0. Epub 2015 Jan 31.
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.
沃纳综合征是一种罕见的常染色体隐性疾病，由人类WRN基因突变引起，其特征是过早出现正常衰老症状。鉴于该疾病患者表现出骨质疏松症，本研究旨在确定WRN基因是否与骨质疏松症的病因有关。在1632例连续的日本尸检中进行了一项关于WRN基因中8个非同义多态性与股骨骨折发生率的基因关联研究，其中140例患者在生前经历过骨折。结果在251名无亲缘关系的绝经后日本骨质疏松症女性和269名非机构化的社区居住日本成年人中得到验证。在rs2230009（c.340G>A）（导致缬氨酸到异亮氨酸的替代）与骨折风险之间观察到统计学上显著的关联；股骨骨折的发生率随A等位基因数量呈剂量依赖性增加（p=0.0120）。如果绝经后骨质疏松症女性和社区居住成年人具有AG而非GG基因型，其股骨颈骨密度和全骨密度分别较低。结果表明，携带WRN基因rs2230009至少一个A等位基因的日本受试者股骨骨折风险显著更高，可能是由于骨密度降低。
