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

详细信息    查看全文

• 作者：Yonghong Li ; Monica Chang ; Olivia Abar ; Veronica Garcia ; Charles Rowl ; Joseph Catanese ; David Ross ; Samuel Broder ; Mitchell Shiffman ; Ramsey Cheung ; Teresa Wright ; Scott L. Friedman ; John Sninsky
• 关键词：Liver fibrosis ; Risk factor ; Single nucleotide polymorphism ; Toll-like receptor TLR4 ; Syntaxin binding protein STXBP5L
• 刊名：Journal of Hepatology
• 出版年：2009
• 出版时间：October 2009
• 年：2009
• 卷：51
• 期：4
• 页码：750-757
• 全文大小：237 K

文摘

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 × 10⁻⁵ and 4.49 × 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.