Low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms are associated with bone mass in both Chinese and whites.

Low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms are associated with bone mass in both Chinese and whites. Research Abstract Details 

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Low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms are associated with bone mass in both Chinese and whites. Abstract Text:

Dong-Hai Xiong,Shu-Feng Lei,Fang Yang,Liang Wang,Yu-Mei Peng,Wei Wang,Robert R Recker,Hong-Wen Deng,

In this study, the associations of novel LRP5 variants with BMD variation were detected and some replicated in the two ethnic groups of Chinese and white origins, respectively. These data support the concept that LRP5 variation can contribute to minor and major variation in bone structure. INTRODUCTION: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene have been shown to cause both high and low bone mass. However, it is still controversial whether LRP5 is associated with normal BMD variation. This study explored the association of LRP5 with BMD phenotypes at three clinically important skeletal sites-the spine, hip, and ultradistal radius (UD)-in two independent populations of Chinese and white ethnicities, respectively. MATERIALS AND METHODS: The Chinese sample consisted of 733 unrelated subjects. The white sample was made up of 1873 subjects from 405 nuclear families. High-density single nucleotide polymorphisms (SNPs) across the whole LRP5 gene were genotyped and analyzed in both samples. RESULTS: Linkage disequilibrium (LD) analyses showed that the haplotype structures of LRP5 between Chinese and whites were in good agreement. Association tests showed that polymorphisms in block 5 spanning intron 7 to intron 19 of LRP5 significantly associated with spine BMD variation in both samples. Particularly, the significant association of SNP rs491347 in intron 7 with spine BMD in the Chinese sample (p=0.002) was replicated in whites, even after adjusting for multiple testing (p=0.005). Its strongly associated SNP rs1784235 could cause the loss of an estrogen receptor alpha (ERalpha) binding site in LRP5, which could partially explain the above replicated association. However, we did not observe any significant replication with BMD variation at the hip and UD. After accounting for multiple testing, associations with BMD variation at these two sites were mainly found in Chinese. Sex-stratified analyses further revealed that the LRP5 associations with BMD in Chinese and whites were driven by male and female subjects, respectively. CONCLUSIONS: Our work supported LRP5 genetic variants as possible susceptibility factors for osteoporosis and fractures in humans. Especially, the SNP rs491347 and its strongly associated SNPs (e.g., rs1784235) could be important to human osteoporosis phenotypes.

Low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms are associated with bone mass in both Chinese and whites. Publishing Authors By Initials

DH Xiong,SF Lei,F Yang,L Wang,YM Peng,W Wang,RR Recker,HW Deng,

For similar genetic phenomena: variation (genetics): polymorphism, genetic: polymorphism, single nucleotide research abstracts see: genetic phenomena: variation (genetics): polymorphism, genetic: polymorphism, single nucleotide research

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Low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms are associated with bone mass in both Chinese and whites. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of bone and mineral research : the officia

VOLUME: 22

Page Numbers: 385-93

Journal Abbreviation: J. Bone Miner. Res.

ISSN: 0884-0431

DAY: 3

MONTH: Mar

YEAR: 2007

Low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms are associated with bone mass in both Chinese and whites. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8610640

Low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms are associated with bone mass in both Chinese and whites. Keywords Mesh Terms:

KEYWORDS: Polymorphism, Single Nucleotide

MESH TERMS: genetics

Chemical & Substance for Abstract: Low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms are associated with bone mass in both Chinese and whites. Information

Substance Name: lipoprotein receptor related protein 5

Registry Number: 0

Grant and Affiliation Information for Low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms are associated with bone mass in both Chinese and whites.

AFFILIATION: Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University, Omaha, NE, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: R01 GM60402-01A1

ACRONYM: GM

MEDLINETA: J Bone Miner Res

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