Association of Low-Density Lipoprotein Receptor-Related Protein 5 (LRP5) Promoter SNP with Peak Bone Mineral Density in Chinese WomenCheung C.-L. · Huang Q.-Y. · Chan V. · Kung A.W.C.
Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
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Objective: Low-density lipoprotein receptor-related protein 5 (LRP5) is important for osteoblast differentiation and mutations of the gene are associated with both low and high bone mass syndromes. Our study aimed to evaluate the importance of LRP5 in the determination of peak bone mass acquisition in Chinese females in the general population. Methods: A total of 286 young southern Chinese females (aged 22–44 years) with low bone mineral density (BMD) (defined by a BMD Z score ≤–1.28 at either the hip or spine) or high BMD (Z score ≧+1) were studied. The LRP5 gene was sequenced for single nucleotide polymorphisms (SNPs) and 4 SNPs were tagged from 8 genotyped SNPs for this study. Results: Single locus allele association tests revealed significant associations of rs682429 and rs686921 with BMD variation (p < 0.05). Omnibus test (likelihood ratio test) revealed overall significant association between LRP5 gene locus and total hip BMD, with rs682429 being most predictive. rs682429 is located in 5′UTR, 2 bases adjacent to a consensus recognition site for the Elk-1 binding element. Conclusion: Common variations of the LRP5 promoter are associated with BMD in young women. These significant associations appear to be driven by rs682429. Functional studies are necessary to elucidate the role of this SNP on the effect of Elk-1 binding element transcriptional activity of LRP5 gene.
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