Pathway-based association analyses identified TRAIL pathway for osteoporotic fractures.

<h4>Introduction</h4>Hip OF carries the highest morbidity and mortality. Previous studies revealed that individual genes/loci in the Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) pathway were associated with bone metabolism. This study aims to verify the potential...

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Autores principales: Yin-Ping Zhang, Yao-Zhong Liu, Yan Guo, Xiao-Gang Liu, Xiang-Hong Xu, Yan-Fang Guo, Yuan Chen, Feng Zhang, Feng Pan, Xue-Zhen Zhu, Hong-Wen Deng
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Publicado: Public Library of Science (PLoS) 2011
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spelling oai:doaj.org-article:0f66d0f5aba4433a891e7ef67052bbc82021-11-18T06:50:32ZPathway-based association analyses identified TRAIL pathway for osteoporotic fractures.1932-620310.1371/journal.pone.0021835https://doaj.org/article/0f66d0f5aba4433a891e7ef67052bbc82011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21760914/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Introduction</h4>Hip OF carries the highest morbidity and mortality. Previous studies revealed that individual genes/loci in the Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) pathway were associated with bone metabolism. This study aims to verify the potential association between hip OF and TRAIL pathway.<h4>Methods</h4>Using genome-wide genotype data from Affymetrix 500 K SNP arrays, we performed novel pathway-based association analyses for hip OF in 700 elderly Chinese Han subjects (350 with hip OF and 350 healthy matched controls).<h4>Results</h4>The TRAIL pathway achieved a significant p value (p = 0.01) for association with hip OF. Among the 38 genes in the TRAIL pathway, seven genes achieved nominally significant association with hip OF (p<0.05); the TNFSF10 (TRAIL) gene obtained the most significant p value (p = 1.70×10(-4)). SNPs (rs719126, rs6533015, rs9594738, rs1805034, rs11160706) from five genes (CFLAR, NFKB1, TNFSF11, TNFRSF11A, TRAF3) of the pathway had minor alleles that appear to be protective to hip OF. SNPs (rs6445063 and rs4259415) from two genes (TNFSF10 and TNFRSF10B) of the pathway had minor alleles (A) that are associated with an increased risk of hip OF, with the ORs (odds ratios) of 16.51 (95%CI:3.83-71.24) and 1.37 (95%CI:1.08-1.74), respectively.<h4>Conclusions</h4>Our study supports the potential role of the TRAIL pathway in the pathogenesis of hip OF in Chinese Han population. Further functional study of this pathway will be pursued to determine the mechanism by which it confers risk to hip OF.Yin-Ping ZhangYao-Zhong LiuYan GuoXiao-Gang LiuXiang-Hong XuYan-Fang GuoYuan ChenFeng ZhangFeng PanXue-Zhen ZhuHong-Wen DengPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 7, p e21835 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yin-Ping Zhang
Yao-Zhong Liu
Yan Guo
Xiao-Gang Liu
Xiang-Hong Xu
Yan-Fang Guo
Yuan Chen
Feng Zhang
Feng Pan
Xue-Zhen Zhu
Hong-Wen Deng
Pathway-based association analyses identified TRAIL pathway for osteoporotic fractures.
description <h4>Introduction</h4>Hip OF carries the highest morbidity and mortality. Previous studies revealed that individual genes/loci in the Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) pathway were associated with bone metabolism. This study aims to verify the potential association between hip OF and TRAIL pathway.<h4>Methods</h4>Using genome-wide genotype data from Affymetrix 500 K SNP arrays, we performed novel pathway-based association analyses for hip OF in 700 elderly Chinese Han subjects (350 with hip OF and 350 healthy matched controls).<h4>Results</h4>The TRAIL pathway achieved a significant p value (p = 0.01) for association with hip OF. Among the 38 genes in the TRAIL pathway, seven genes achieved nominally significant association with hip OF (p<0.05); the TNFSF10 (TRAIL) gene obtained the most significant p value (p = 1.70×10(-4)). SNPs (rs719126, rs6533015, rs9594738, rs1805034, rs11160706) from five genes (CFLAR, NFKB1, TNFSF11, TNFRSF11A, TRAF3) of the pathway had minor alleles that appear to be protective to hip OF. SNPs (rs6445063 and rs4259415) from two genes (TNFSF10 and TNFRSF10B) of the pathway had minor alleles (A) that are associated with an increased risk of hip OF, with the ORs (odds ratios) of 16.51 (95%CI:3.83-71.24) and 1.37 (95%CI:1.08-1.74), respectively.<h4>Conclusions</h4>Our study supports the potential role of the TRAIL pathway in the pathogenesis of hip OF in Chinese Han population. Further functional study of this pathway will be pursued to determine the mechanism by which it confers risk to hip OF.
format article
author Yin-Ping Zhang
Yao-Zhong Liu
Yan Guo
Xiao-Gang Liu
Xiang-Hong Xu
Yan-Fang Guo
Yuan Chen
Feng Zhang
Feng Pan
Xue-Zhen Zhu
Hong-Wen Deng
author_facet Yin-Ping Zhang
Yao-Zhong Liu
Yan Guo
Xiao-Gang Liu
Xiang-Hong Xu
Yan-Fang Guo
Yuan Chen
Feng Zhang
Feng Pan
Xue-Zhen Zhu
Hong-Wen Deng
author_sort Yin-Ping Zhang
title Pathway-based association analyses identified TRAIL pathway for osteoporotic fractures.
title_short Pathway-based association analyses identified TRAIL pathway for osteoporotic fractures.
title_full Pathway-based association analyses identified TRAIL pathway for osteoporotic fractures.
title_fullStr Pathway-based association analyses identified TRAIL pathway for osteoporotic fractures.
title_full_unstemmed Pathway-based association analyses identified TRAIL pathway for osteoporotic fractures.
title_sort pathway-based association analyses identified trail pathway for osteoporotic fractures.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/0f66d0f5aba4433a891e7ef67052bbc8
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