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

白细胞介素 28B 上游的单核苷酸多态性与 HCV 基因 1 型感染患者早期病毒动力学的第 1 期和第 2 期相关

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Abstract

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.

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