Endochondral ossification pathway genes and postmenopausal osteoporosis: Association and specific allele related serum bone sialoprotein levels in Han Chinese.

Yunzhi Zhang,KunZheng Wang,Lu Li,Tianxiao Zhang,Dongke Fu,Chen Zhang,Gang Chen,Haiyan Liu,Bo Zhang

doi:10.1038/srep16783

Abstract

Osteoporosis is a systemic skeletal disorder characterized by reduced bone mineral density (BMD) and disrupted bone architecture, predisposing the patient to increased fracture risk. Evidence from early genetic epidemiological studies has indicated a major role for genetics in the development of osteoporosis and the variation in BMD. In this study, we focused on two key genes in the endochondral ossification pathway, IBSP and PTHLH. Over 9,000 postmenopausal Han Chinese women were recruited, and 54 SNPs were genotyped. Two significant SNPs within IBSP, rs1054627 and rs17013181, were associated with BMD and postmenopausal osteoporosis by the two-stage strategy, and rs17013181 was also significantly associated with serum IBSP levels. Moreover, one haplotype (rs12425376-rs10843047-rs42294) covering the 5’ end of PTHLH was associated with postmenopausal osteoporosis. Our results provide evidence for the association of these two key endochondral ossification pathway genes with BMD and osteoporosis in postmenopausal Han Chinese women. Combined with previous findings, we provide evidence that a particular SNP in IBSP has an allele-specific effect on mRNA levels, which would, in turn, reflect serum IBSP levels.

Highlights

To be associated with bone mineral density (BMD) or OP13
To comprehensively investigate the susceptibility of genes involved in the endochondral ossification pathway, we examined the relationship between the two key genes IBSP and PTHLH and the diagnosis status of OP in over 9,000 postmenopausal women from the Han Chinese population
We identified some significant haplotypes in the IBSP gene and the PTHLH gene

Summary

Introduction

To be associated with BMD or OP13. Despite these attempts of association mapping based on common SNPs, the percentage of phenotypic variance explained by all these loci is still modest[13,14]. Unidirectional allele-specific regulation (ASE) of IBSP has been reported in human bone samples, with lower expression of the G allele compared to the A allele for SNP rs1701318117. It is still unclear whether the association of IBSP with BMD exists in a genetically independent Han Chinese population, and whether a similar allele-specific pattern identified at the RNA level would reflect serum protein levels. To comprehensively investigate the susceptibility of genes involved in the endochondral ossification pathway, we examined the relationship between the two key genes IBSP and PTHLH and the diagnosis status of OP in over 9,000 postmenopausal women from the Han Chinese population. To determine whether the significant variants of OP are related to serum integrin-binding sialoprotein (IBSP, encoded by gene IBSP) levels, we measured IBSP serum levels in all of the samples

Methods

Results

Discussion

Conclusion