Single nucleotide polymorphism upstream of interleukin 28B associated with phase 1 and phase 2 of early viral kinetics in patients infected with HCV genotype 1

被引：27

作者：

Howell, Charles D. ^{[1
]}

Gorden, Alexis ^{[1
]}

Ryan, Kathleen A. ^{[1
]}

Thompson, Alexander J. ^{[2
,3
]}

Ibrahim, Chadi ^{[1
,4
]}

Fried, Michael ^{[5
]}

Afdhal, Nezam H. ^{[6
]}

McHutchison, John G. ^{[2
,3
]}

Shianna, Kevin V. ^{[7
]}

Goldstein, David B. ^{[7
]}

Shuldiner, Alan R. ^{[1
]}

Mitchell, Braxton D. ^{[1
]}

机构：

[1] Univ Maryland, Sch Med, Program Genet & Genom Med, Baltimore, MD 21201 USA

[2] Duke Univ, Div Gastroenterol, Durham, NC USA

[3] Duke Univ, Duke Clin Res Inst, Durham, NC USA

[4] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA

[5] Univ N Carolina, Chapel Hill, NC USA

[6] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA

[7] Duke Univ, Ctr Human Genome Variat, Inst Genome Sci & Policy, Durham, NC USA

来源：

JOURNAL OF HEPATOLOGY | 2012年 / 56卷 / 03期

关键词：

IL28B gene; Hepatitis C virus; Viral kinetics; Single nucleotide polymorphism;

D O I：

10.1016/j.jhep.2011.10.004

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background & Aims: We studied the relationship between IL28B gene-related SNP rs12979860 and early viral kinetics (day 0-28) during peginterferon and ribavirin treatment, in 173 African Americans (AA) and 188 Caucasian Americans (CA) with HCV genotype 1. Methods: We studied the relationship between IL28B 16 gene-related SNP rs12979860 and early viral kinetics (day 0-28) 17 during peginterferon and ribavirin treatment, in 171 African 18 Americans (AA) and 188 Caucasian Americans (CA) with HCV 19 genotype 1. Results: Compared to non-C/C genotypes, C/C was associated with greater declines in serum HCV RNA during phase 1 (day 0-2), phase 2 (day 7-28), and day 0-28 and higher response (undetected HCV RNA) rates at weeks 4 and 12 in AA and CA. A static phase and increases in HCV RNA from day 2 to 7 were more common in patients with non-C/C genotypes. C/C was also associated with higher week 24, 48, and 72 response rates in CA (p<0.01) but not in AA. At baseline, SNP genotype was the only independent predictor of phase 1; SNP genotype and phase 1 were independent predictors of phase 2 (p<0.001). There were no racial differences in HCV RNA declines during phase 1, day 2-7, phase 2, and day 0-28 with the same SNP genotype. AA with C/C and C/T genotypes had lower week 24, 48, and 72 (SVR) rates than did CA (p = 0.03). SNP C/C predicted higher SVR rates in AA and CA with high baseline HCV RNA (>= 600,000 IU/ml), and in CA with >= 1 log(10) IU/ml decrease in HCV RNA from day 0 to 28. Conclusions: SNP rs12979860 is strongly associated with both phase 1 and phase 2 HCV RNA kinetics in AA and CA with HCV genotype 1. (C) 2012 Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.

引用

页码：557 / 563

页数：7

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