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Meta-Analysis
. 2020 Apr:133:115247.
doi: 10.1016/j.bone.2020.115247. Epub 2020 Jan 20.

Identification of PIEZO1 polymorphisms for human bone mineral density

Wei-Yang Bai  1 , Lijun Wang  2 , Zhi-Min Ying  3 , Bin Hu  3 , Lin Xu  4 , Guo-Qing Zhang  1 , Pei-Kuan Cong  1 , Xiaofeng Zhu  5 , Weiguo Zou  6 , Hou-Feng Zheng  7
Affiliations
Meta-Analysis

Identification of PIEZO1 polymorphisms for human bone mineral density

Wei-Yang Bai et al. Bone. 2020 Apr.

Abstract

Bone mineral density (BMD) is a key indicator for diagnosis and treatment for osteoporosis; the reduction of BMD could increase the risk of osteoporotic fracture. It was very recently found that Piezo1 mediated mechanically evoked responses in bone and further participated in bone formation in mice. Here, we performed cross phenotype meta-analysis for human BMD at lumbar spine (LS), femoral neck (FN), distal radius/forearm (FA) and heel and screened out 14 top SNPs for PIEZO1, these SNPs were overlapped with putative enhancers, DNase-I hypersensitive sites and active promoter flanking regions. We found that the signal of the best SNP rs62048221 was mainly from heel ultrasound estimated BMD (-0.02 SD per T allele, P = 8.50E-09), where calcaneus supported most of the mechanical force of body when standing, walking and doing physical exercises. Each copy of the effect allele T of SNP rs62048221 was associated with a decrease of 0.0035 g/cm2 BMD (P = 4.6E-27, SE = 0.0003) in UK Biobank data within 477,760 samples. SNP rs62048221 was located at the enhancer region (HEDD enhancer ID 2331049) of gene PIEZO1, site-directed ChIP assays in human mesenchymal stem cells (hMSCs) showed significant enrichment of H3K4me1 and H3K27ac in this region, luciferase assays showed that rs62048221 could significantly affect the activity of the enhancer where it resides. Our results first suggested that SNP rs62048221 might mediate the PIEZO1 expression level via modulating the activity of cis-regulatory elements and then further affect the BMD.

Keywords: Bone mineral density; Mechanical force; PIEZO1; Polymorphism; Regulation.

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Conflict of interest statement

Declaration of competing interest None of the authors of this paper has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of the paper.

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