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. 2009 Oct;51(4):750-7.
doi: 10.1016/j.jhep.2009.04.027. Epub 2009 Jun 18.

Multiple variants in toll-like receptor 4 gene modulate risk of liver fibrosis in Caucasians with chronic hepatitis C infection

Yonghong Li  1 , Monica Chang, Olivia Abar, Veronica Garcia, Charles Rowland, Joseph Catanese, David Ross, Samuel Broder, Mitchell Shiffman, Ramsey Cheung, Teresa Wright, Scott L Friedman, John Sninsky
Affiliations

Multiple variants in toll-like receptor 4 gene modulate risk of liver fibrosis in Caucasians with chronic hepatitis C infection

Yonghong Li et al. J Hepatol. 2009 Oct.

Abstract

Background/aims: 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.

Methods: We carried out dense genotyping and association testing of additional SNPs in each of the 7 regions in Caucasian case control samples.

Results: 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 x 10(-5) and 4.49 x 10(-6), respectively).

Conclusions: 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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Figures

Fig. 1
Fig. 1
Fine-mapping analysis of the TLR4 locus. (A) Linkage disequilibrium structure in the HapMap CEPH dataset and gene location are shown. (B) Allelic association of single SNPs with fibrosis risk. The broken line denotes P = 0.05.
See this image and copyright information in PMC

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