Identification of non-synonymous polymorphisms in the WDSOF1 gene as novel susceptibility markers for low bone mineral density in Japanese postmenopausal women

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• 作者：Tomohiko Urano ; Masataka Shiraki ; Takahiko Usui ; Noriko Sasaki ; Yasuyoshi Ouchi ; Satoshi Inoue
• 关键词：WDSOF1 ; Single-nucleotide polymorphisms ; Bone mineral density ; Osteoporosis
• 刊名：Bone
• 出版年：2010
• 出版时间：September 2010
• 年：2010
• 卷：47
• 期：3
• 页码：636-642
• 全文大小：621 K

文摘

Genetic factors are important for the development of osteoporosis. During the search for novel markers of single-nucleotide polymorphisms (SNPs) associated with bone mineral density (BMD) by performing a large-scale SNP screen with 251 Japanese postmenopausal women utilizing 50K SNP array, we here focused on the rs1370005 in the WD repeats and SOF1 domain-containing (WDSOF1) gene because we could found common non-synonymous variants in this WDSOF1 gene. The analysis of linkage disequilibrium (LD) in the WDSOF1 gene revealed that rs1370005 and 3 other non-synonymous SNPs (Arg47Ser, Pro108Leu and Ile194Val) lie in a 30-kb region of high LD. Quantitative real-time PCR (qRT-PCR) analysis showed that WDSOF1 mRNA was expressed in mouse primary osteoblasts and osteoclasts, suggesting that WDSOF1 plays some roles in the bone metabolism. We examined the 3 non-synonymous SNPs in WDSOF1 gene in 750 Japanese postmenopausal women. A trend test showed that Arg47Ser, Pro108Leu, and Ile194Val genotypes were significant associated with total body BMD (Arg47Ser; P = 0.021, Pro108Leu; P = 0.022 and Ile194Val; P = 0.009). We also compared Z scores for total body BMD between the subjects bearing at least one minor allele and those lacking the minor allele using unpaired t test. Subjects with the one or two minor alleles had significantly lower Z scores for total body BMD (Arg47Ser; P = 0.010, Pro108Leu; P = 0.019 and Ile194Val; P = 0.003). The present study suggests that these non-synonymous WDSOF1 polymorphisms play a role in the genetic susceptibility to osteoporosis.