IFNL3 (IL28B) and IFNL4 polymorphisms are associated with treatment response in Thai patients infected with HCV genotype 1, but not with genotypes 3 and 6.
Recent studies have shown an association between single nucleotide polymorphisms (SNPs) in the interferon lambda-3 (IFNL3 or IL-28B) and IFNL4 genes and treatment response to hepatitis C virus genotype 1 (HCV-1) infection. The importance of these SNPs for HCV genotype 3 (HCV-3), and particularly HCV genotype 6 (HCV-6), remains to be elucidated. We analyzed a cohort of 225 Thai individuals with chronic HCV infection treated with pegylated-interferon and ribavirin, of whom 69 (30.7%), 114 (50.7%) and 42 (18.6%) patients were infected with HCV-1, HCV-3, and HCV-6, respectively. DNA extracted from blood samples was analyzed for the SNPs rs12979860 and ss469415590. The distribution of CC, CT, and TT genotypes of rs12979860 was 189 (84%), 28 (12.4%) and 8 (3.6%), respectively, while the distribution of TT/TT, ΔG/TT, and ΔG/ΔG genotypes of ss469415590 was 192(85.3%), 28(12.5%), and 5(2.2%), respectively. Significantly lower frequencies of the favorable genotypes CC (for rs12979860) and TT/TT (for ss469415590) were found in the HCV-1 group in comparison with the other groups. The favorable genotypes were associated significantly with rapid and sustained virological response in the HCV-1 group. However, they were only associated with rapid virological response in the HCV-3 and HCV-6 groups. Furthermore, both SNPs were associated equally with the treatment outcome in the HCV-1 group. In contrast, the role of these SNPs in predicting treatment response was attenuated in the HCV-3 and HCV-6 groups. Thus, identification of these SNPs may be useful only in patients with refractory HCV-1 infection.
Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Srunthron
S
Akkarathamrongsin
Vo Duy
VD
Thong
Sunchai
S
Payungporn
Kittiyod
K
Poovorawan
Phisit
P
Prapunwattana
Yong
Y
Poovorawan
Pisit
P
Tangkijvanich
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D013785:Thailand; D016896:Treatment Outcome; D000095022:Interferon Lambda
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C579163:IFNL4 protein, human; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a
interferon lambda-3; interferon lambda-4; interleukin 28B; single nucleotide polymorphisms; sustained virological response