A missense single nucleotide polymorphism, V114I of the Werner syndrome gene, is associated with risk of osteoporosis and femoral fracture in the Japanese
A missense single nucleotide polymorphism, V114I of the Werner syndrome gene, is associated with risk of osteoporosis and femoral fracture in the Japanese
复制标题
维尔纳综合征基因的错义单核苷酸多态性 V114I 与日本人骨质疏松和股骨骨折的风险相关
DOI：
10.1007/s00774-014-0636-0
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Ito H.
中科院分区：
文献类型：
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作者：
Zhou H;Mori S;Tanaka M;Sawabe M;Arai T;Muramatsu M;Mieno MN;Shinkai S;Yamada Y;Miyachi M;Murakami H;Sanada K;Ito H.
Werner综合征是一种罕见的常染色体隐性遗传病，由人类wrngene突变引起，其特征是正常衰老症状的早期发作。鉴于这种疾病的患者表现为骨质疏松症，本研究旨在确定wrngene是否与骨质疏松症的病因有关。对日本1632例连续尸检（其中140例患者在其一生中经历过骨折）进行了wrngene 8个非同义多态性与股骨骨折发生率的遗传关联研究。研究结果在251名无关联的日本绝经后骨质疏松症妇女和269名非住院的日本社区成年人中得到了验证。rs2230009 (c.340G > A)（导致Val to Ile替代）与骨折风险之间存在统计学上显著的关联；股骨骨折发生率随A等位基因数量呈剂量依赖性增加（p= 0.0120）。绝经后骨质疏松症妇女和社区居民的股骨颈骨和全骨密度分别较低，如果她们是AG而不是GG基因型。结果表明，携带wrn9基因rs2230009至少一个A等位基因的日本受试者发生股骨骨折的风险明显更高，可能是由于骨密度降低。
Werner syndrome is a rare autosomal recessive disorder caused by mutations in the humanWRNgene 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 theWRNgene contributes to the etiology of osteoporosis. A genetic association study of eight non-synonymous polymorphisms in theWRNgene 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 theWRNgene are at a significantly higher risk of femoral fracture, possibly due to decreased bone density.