Document Detail


Association of a single-nucleotide variation (A1330V) in the low-density lipoprotein receptor-related protein 5 gene (LRP5) with bone mineral density in adult Japanese women.
MedLine Citation:
PMID:  17306638     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Low-density lipoprotein receptor-related protein 5 (LRP5), a co-receptor of Wnt signaling, is an important regulator of bone development and maintenance. Recently we identified correlation between an intronic single-nucleotide polymorphism (SNP) in the LRP5 gene and vertebral bone mineral density (BMD), indicating that a genetic ground exists at this locus for determination of BMD. In the study reported here, we searched for nucleotide variation(s) that might confer susceptibility to osteoporosis among an extended panel of 387 healthy subjects recruited from the same hospital (Group-A), as well as among 384 subjects from the general population in eastern Japan (Group-B). We basically focused on two potentially functional variations, Q89R (c.266A > G) and A1330V (c.3989C > T), whose functional effects by the amino-acid changes were estimated by the SIFT software program; it predicted the 1330 V allele as deleterious ("intolerant") although the minor allele of Q89R was questionable. By analyzing associations between the variant alleles and the BMD, reproducible association of the minor variant of A1330V to lower adjusted BMD levels was detected; i.e., In Group-A subjects 1330-V significantly associated with the spinal BMD Z-score (P = 0.034), and in Group-B it associated with low radial BMD (P = 0.019). From haplotype and linkage disequilibrium (LD) analysis for 29 SNPs, we detected two separate LD blocks within the entire 137-kb LRP5 locus, basically consistent with a previous report on Caucasians. One of the second block haplotype significantly associated with adjusted BMD (r = 0.15, P = 0.004). Possible combined effect of Q89R and A1330V belonging to different LD blocks was denied by multiple regression analyses. Our results indicate that genetic variations in LRP5 are important factors affecting BMD in adult women and that 1330 V may contribute to osteoporosis susceptibility, at least in Japanese.
Authors:
Yoichi Ezura; Toshiaki Nakajima; Tomohiko Urano; Yoshihiro Sudo; Mitsuko Kajita; Hideyo Yoshida; Takao Suzuki; Takayuki Hosoi; Satoshi Inoue; Masataka Shiraki; Mitsuru Emi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-02-15
Journal Detail:
Title:  Bone     Volume:  40     ISSN:  8756-3282     ISO Abbreviation:  Bone     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-03-16     Completed Date:  2007-06-07     Revised Date:  2011-02-02    
Medline Journal Info:
Nlm Unique ID:  8504048     Medline TA:  Bone     Country:  United States    
Other Details:
Languages:  eng     Pagination:  997-1005     Citation Subset:  IM    
Affiliation:
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, 1-396, Kosugi-cho, Nakahara-ku, Kawasaki 211-8533, Japan. ezura.mph@mri.tmd.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Alleles
Bone Density / genetics*
Female
Gene Frequency
Genetic Variation
Haplotypes
Humans
Japan
LDL-Receptor Related Proteins / genetics*
Linkage Disequilibrium
Middle Aged
Osteoporosis / etiology,  genetics
Polymorphism, Single Nucleotide*
Quantitative Trait Loci
Chemical
Reg. No./Substance:
0/LDL-Receptor Related Proteins; 0/low density lipoprotein receptor-related protein 5

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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