Identification of a single nucleotide polymorphism in the MxA gene promoter (G/T at nt -88) correlated with the response of hepatitis C patients to interferon.
The interferon (IFN)-inducible MxA protein is known to play an important role in the host defense against certain viruses. We aimed to see if any genetic polymorphism in the promoter region of the MxA gene is associated with the IFN responsiveness of hepatitis C virus (HCV)-infected patients. Initially we sequenced the promoter region of the MxA gene in 12 subjects and found a polymorphic site. We then constructed a specific PCR-RFLP system for this site and subjected 63 samples from chronic hepatitis C patients who were nonresponders (NR) to IFN therapy to it, 52 with sustained response (SR), and 42 healthy controls. Subjects were all Japanese, and unrelated. A single nucleotide polymorphism (SNP) was identified in the MxA promoter region: G/T alleles at nt position -88. Interestingly, this SNP was involved in a genetic element highly homologous to the IFN-stimulated response element consensus sequence, and the G-to-T change there makes this homology a little greater. The rate of G.G homozygosity was 31% in the SR patients, significantly lower than in the NR patients (62%, p = 0.0009), while that of healthy controls was between the two groups (48%). Differences in HCV genotypes did not influence this result. Based on these findings, we propose that the SNP of the MxA promoter at nt -88 identified in this study affects the expression of MxA protein, and may thus be associated with the response of HCV patients to IFN.
Hijikata
M
M
Department of Medical Sciences, Toshiba General Hospital, Shinagawa-ku, Tokyo, Japan.
Ohta
Y
Y
Mishiro
S
S
D000998:Antiviral Agents / Q000627:therapeutic use*; D001483:Base Sequence; D019204:GTP-Binding Proteins; D016174:Hepacivirus / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D064547:Myxovirus Resistance Proteins; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D016896:Treatment Outcome
D000998:Antiviral Agents; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D007372:Interferons; D019204:GTP-Binding Proteins