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Differential gene expression orchestrated by transcription factors in osteoporosis: bioinformatics analysis of associated polymorphism elaborating functional relationships

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 osteo...

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Autores principales: Wang, Chih-Chien, Weng, Jen-Jie, Chen, Hsiang-Cheng, Lee, Meng-Chang, Ko, Pi-Shao, Su, Sui-Lung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271311/
https://www.ncbi.nlm.nih.gov/pubmed/35748775
http://dx.doi.org/10.18632/aging.204136
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author Wang, Chih-Chien
Weng, Jen-Jie
Chen, Hsiang-Cheng
Lee, Meng-Chang
Ko, Pi-Shao
Su, Sui-Lung
author_facet Wang, Chih-Chien
Weng, Jen-Jie
Chen, Hsiang-Cheng
Lee, Meng-Chang
Ko, Pi-Shao
Su, Sui-Lung
author_sort Wang, Chih-Chien
collection PubMed
description 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 A4GALT 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.
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spelling pubmed-92713112022-07-13 Differential gene expression orchestrated by transcription factors in osteoporosis: bioinformatics analysis of associated polymorphism elaborating functional relationships Wang, Chih-Chien Weng, Jen-Jie Chen, Hsiang-Cheng Lee, Meng-Chang Ko, Pi-Shao Su, Sui-Lung Aging (Albany NY) Research Paper 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 A4GALT 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. Impact Journals 2022-06-21 /pmc/articles/PMC9271311/ /pubmed/35748775 http://dx.doi.org/10.18632/aging.204136 Text en Copyright: © 2022 Wang et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Wang, Chih-Chien
Weng, Jen-Jie
Chen, Hsiang-Cheng
Lee, Meng-Chang
Ko, Pi-Shao
Su, Sui-Lung
Differential gene expression orchestrated by transcription factors in osteoporosis: bioinformatics analysis of associated polymorphism elaborating functional relationships
title Differential gene expression orchestrated by transcription factors in osteoporosis: bioinformatics analysis of associated polymorphism elaborating functional relationships
title_full Differential gene expression orchestrated by transcription factors in osteoporosis: bioinformatics analysis of associated polymorphism elaborating functional relationships
title_fullStr Differential gene expression orchestrated by transcription factors in osteoporosis: bioinformatics analysis of associated polymorphism elaborating functional relationships
title_full_unstemmed Differential gene expression orchestrated by transcription factors in osteoporosis: bioinformatics analysis of associated polymorphism elaborating functional relationships
title_short Differential gene expression orchestrated by transcription factors in osteoporosis: bioinformatics analysis of associated polymorphism elaborating functional relationships
title_sort differential gene expression orchestrated by transcription factors in osteoporosis: bioinformatics analysis of associated polymorphism elaborating functional relationships
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271311/
https://www.ncbi.nlm.nih.gov/pubmed/35748775
http://dx.doi.org/10.18632/aging.204136
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