Differential Gene Expression Orchestrated by Transcription Factors in Osteoporosis: Bioinformatics Analysis of Associated Polymorphism Elaborating Functional Relationships

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2022 Jun 24

PMID 35748775

Authors

Chih-Chien Wang

Jen-Jie Weng

Hsiang-Cheng Chen

Meng-Chang Lee

Pi-Shao Ko

Sui-Lung Su

Affiliations

Soon will be listed here.

Abstract

Background: Identification of candidate SNPs from transcription factors (TFs) is a novel concept, while systematic large-scale studies on these SNPs are scarce.

Purpose: This study aimed to identify the SNPs of six TF binding sites (TFBSs) and examine the association between candidate SNPs and osteoporosis.

Methods: We used the Taiwan BioBank database; University of California, Santa Cruz, reference genome; and a chromatin immunoprecipitation sequencing database to detect 14 SNPs at the potential binding sites of six TFs. Moreover, we performed a case-control study and genotyped 109 patients with osteoporosis (T-score ≤ -2.5 evaluated by dual-energy X-ray absorptiometry) and 262 healthy individuals (T-score ≥ -1) at Tri-Service General Hospital from 2015 to 2019. Furthermore, we used the expression quantitative trait loci (eQTL) from the Genotype-Tissue Expression database to identify downstream gene expression as a criterion for the function of candidate SNPs.

Results: Bioinformatic analysis identified 14 SNPs of TFBSs influencing osteoporosis. Of these SNPs, the rs130347 CC + TC genotype had 0.57 times higher risk than the TT genotype (OR = 0.57, p = 0.031). Validation of eQTL analysis revealed that rs130347 T allele influences mRNA expression of downstream in whole blood (p = 0.0041) and skeletal tissues (p = 0.011).

Conclusions: We successfully identified the unique osteoporosis locus rs130347 in the Taiwanese and functionally validated this finding. In the future, this strategy can be expanded to other diseases to identify susceptible loci and achieve personalized precision medicine.

Citing Articles

Integrated single-cell and bulk RNA sequencing analysis reveal immune-related biomarkers in postmenopausal osteoporosis.

Fang S, Ni H, Zhang Q, Dai J, He S, Min J Heliyon. 2024; 10(18):e38022.

PMID: 39328516 PMC: 11425179. DOI: 10.1016/j.heliyon.2024.e38022.

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