Association of Low-Density Lipoprotein Receptor-Related Protein 5 (LRP5) Promoter SNP with Peak Bone Mineral Density in Chinese Women

Abstract

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.

A Haplotype-Based Analysis of the LRP5 Gene in Relation to Osteoporosis Phenotypes in Spanish Postmenopausal Women

“…In addition, rs682429 was associated with hip BMD. (17,43) This would be consistent with variants within this block being involved in determining bone phenotypes. The fact that we found a stronger association for SNP 1 than for its haplotype block and that SNP 1 lies within a RUNX2 binding site, suggests that it could be a functional SNP.…”

“…Moreover, although these SNPs are missense, their functionality has not been experimentally proven. A new approach, based on whole gene variation, has been adopted in recent studies. Some such studies analyzed the haplotypic block structure, allowing the use of a limited set of tag‐SNPs to evaluate all the variability within the blocks, as done here. In general, the block structure was quite similar among studies.…”

Associations of apolipoprotein E and low‐density lipoprotein receptor‐related protein 5 polymorphisms with dyslipidemia and generalized aggressive periodontitis in a Chinese population

“…The strengths of our study include: the novelty of our research question, the consistency in genotyping with previous studies, and the comparability of our results. In general, the polymorphisms and allele frequencies of both APOE and LRP5 were similar to those of previous studies among the Chinese population (61)(62)(63). The allele APOE e2 has a cytosine-to-thymine base-pair substitution in rs7412, whilst in APOE e4, a thymine is replaced with a cytosine in rs429358 (64).…”

Genetics of osteoporosis in Chinese

“…We observed the associations of BMD with these two polymorphisms in 674 subjects from 177 families as well 23 . Besides, we also found an association between SNP rs682429 and BMD, but this finding was not replicated by Xiong et al 38,40 . They studied 29 SNPs of LRP5 gene in 733 random Chinese and found the significant association of SNP rs491347 in intron 7 with spine BMD in both Chinese and Whites 38 .…”