The detection of IRF-1 promoter polymorphisms and their possible contribution to T helper 1 response in chronic hepatitis C.
We described the interferon (IFN) regulatory factor-1 (IRF-1) promoter single nucleotide polymorphisms (SNPs), and the clinical and immunologic implications of these SNPs have been investigated. We successfully determined the mutation at -300 of the IRF-1 promoter by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and this mutation linked with other mutations in the promoter region. In our Japanese population, the frequency of the type -300*A/A was 11.9%, type A/G was 54.2%, and type G/G was 33.9%. We found no significant difference without IFN stimulation in the production levels of IFN-gamma and interleukin-10 (IL-10) from peripheral blood mononuclear cells (PBMC) between subjects with -300*A/A and those with other types. IFN-alpha stimulation, however, increased the levels of IFN-gamma significantly and decreased the IL-10 production level significantly only in the subject with -300*A/A type. Flow cytometric analysis showed that the Th1-type CD4(+) cell population was significantly increased by IFN-beta administration only in the patient with chronic hepatitis C with -300*A/A type. These results suggest that the IRF-1 promoter SNP types are positively involved in Th1-type response and, consequently, the -300*A/A type may be beneficial for viral elimination in chronic hepatitis C and IFN therapy.
Saito
Hidetsugu
H
Department of Internal Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan. hsaito@sc.tc.keio.ac.jp
Tada
Shinichiro
S
Wakabayashi
Kanji
K
Nakamoto
Nobuhiro
N
Takahashi
Masahiko
M
Nakamura
Mitsuyasu
M
Ebinuma
Hirotoshi
H
Ishii
Hiromasa
H
D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D005787:Gene Frequency; D006239:Haplotypes; D019698:Hepatitis C, Chronic / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D050856:Interferon Regulatory Factor-1; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use; D016899:Interferon-beta / Q000494:pharmacology / Q000627:therapeutic use; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008113:Liver Neoplasms / Q000473:pathology; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D016898:Interferon-alpha; D010750:Phosphoproteins; D016753:Interleukin-10; D016899:Interferon-beta; D007371:Interferon-gamma