Identification of non-synonymous polymorphisms in the WDSOF1 gene as novel susceptibility markers for low bone mineral density in Japanese postmenopausal women.
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.
Urano
Tomohiko
T
Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Shiraki
Masataka
M
Usui
Takahiko
T
Sasaki
Noriko
N
Ouchi
Yasuyoshi
Y
Inoue
Satoshi
S
D000368:Aged; D000818:Animals; D044466:Asian People / Q000235:genetics*; D015519:Bone Density / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D051379:Mice; D046228:Microarray Analysis; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D011446:Prospective Studies; D011506:Proteins / Q000235:genetics*
D005819:Genetic Markers; D011506:Proteins