Multiple variants in toll-like receptor 4 gene modulate risk of liver fibrosis in Caucasians with chronic hepatitis C infection.
Multiple variants in toll-like receptor 4 gene modulate risk of liver fibrosis in Caucasians with chronic hepatitis C infection.
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DOI：
10.1016/j.jhep.2009.04.027
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发表时间：
2009-10
影响因子：
25.7
通讯作者：
Sninsky J
中科院分区：
文献类型：
--
作者：
Li Y;Chang M;Abar O;Garcia V;Rowland C;Catanese J;Ross D;Broder S;Shiffman M;Cheung R;Wright T;Friedman SL;Sninsky J
最近，与单核苷酸多态性（snp）相关的7个基因组位点与慢性丙型肝炎病毒患者进展为晚期纤维化（纤维化风险）相关。这些基因座中的其他变异尚未被检查，但可能与纤维化风险相关，独立于或由于与原始多态性的连锁不平衡。我们在高加索病例对照样本的7个区域进行了密集的基因分型和关联检测。我们在toll样受体4 （TLR4）和syntaxin结合蛋白5样（STXBP5L）位点中发现了几个与纤维化风险相关的snp，这些snp独立于原始的显著snp。由TLR4和STXBP5L中这些snp组成的单倍型与纤维化风险密切相关（总体P值分别为3.04 × 10 - 5和4.49 × 10 - 6）。TLR4和STXBP5L基因的多种变异调节肝纤维化的风险。这些发现对于理解hcv诱导的白种人肝脏疾病的发病机制具有重要意义，也可能扩展到其他种族。
Seven genomic loci, implicated by single nucleotide polymorphisms (SNPs), have recently been associated with progression to advanced fibrosis (fibrosis risk) in patients with chronic hepatitis C virus. Other variants in these loci have not been examined but may be associated with fibrosis risk independently of or due to linkage disequilibrium with the original polymorphisms. We carried out dense genotyping and association testing of additional SNPs in each of the 7 regions in Caucasian case control samples. We identified several SNPs in the toll-like receptor 4 (TLR4) and syntaxin binding protein 5-like (STXBP5L) loci that were associated with fibrosis risk independently of the original significant SNPs. Haplotypes consisting of these SNPs in TLR4 and STXBP5L were strongly associated with fibrosis risk (global P = 3.04 × 10−5 and 4.49 × 10−6, respectively). Multiple variants in TLR4 and STXBP5L genes modulate risk of liver fibrosis. These findings are of relevance for understanding the pathogenesis of HCV-induced liver disease in Caucasians and may be extended to other ethnicities as well.
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Toll样受体4的肝硬化预测单核苷酸多态性与肝星状细胞反应的功能联系。
影响因子：
13.5
作者：
Guo, Jinsheng;Loke, Johnny;Zheng, Feng;Hong, Feng;Yea, Steven;Fukata, Masayuki;Tarocchi, Mirko;Abar, Olivia T.;Huang, Hongjin;Sninsky, John J.;Friedman, Scott L.
通讯作者：
Friedman, Scott L.
DOI：
10.1056/nejmoa0802629
发表时间：
2008-10-23
期刊：
The New England journal of medicine
影响因子：
--
作者：
Bochud PY;Chien JW;Marr KA;Leisenring WM;Upton A;Janer M;Rodrigues SD;Li S;Hansen JA;Zhao LP;Aderem A;Boeckh M
通讯作者：
Boeckh M
影响因子：
5.7
作者：
Ferwerda, Bart;McCall, Matthew B. B.;Netea, Mihai G.
通讯作者：
Netea, Mihai G.
DOI：
10.1073/pnas.0403535101
发表时间：
2004-11-02
影响因子：
11.1
作者：
Li, Y;Nowotny, P;Grupe, A
通讯作者：
Grupe, A
影响因子：
13.5
作者：
Huang, Honjin;Shiffman, Mitchefl L.;Cheung, Ramsey C.
通讯作者：
Cheung, Ramsey C.