A single nucleotide polymorphism of the low molecular mass polypeptide 7 gene influences the interferon response in patients with chronic hepatitis C


Dr Norio Hayashi, Department of Molecular Therapeutics (G2), Osaka University Graduate School of Medicine, 2–2 Yamadaoka, Suita, Osaka 565–0871, Japan. E-mail: hayashin@moltx.med.osaka-u.ac.jp


summary. Transporter associated with antigen processing (TAP) and low molecular mass polypeptides (LMP) play crucial roles in the human leukocyte antigen (HLA) class I-restricted antigen presenting systems. This study was performed to elucidate whether these antigen-presenting gene polymorphisms could influence the response to interferon (IFN) treatment in patients with chronic hepatitis C. Polymorphisms of TAP and LMP genes in 175 hepatitis C virus (HCV) patients were determined by polymerase chain reaction-restriction fragment length polymorphism. The frequencies of these genes were compared between sustained-responders (n=49) and nonresponders (n=126), classified by biochemical and virological responses to IFN. The distributions of TAP1*, TAP2*, and LMP2 genes between sustained-responders and nonresponders did not differ. However, LMP7-K gene frequency in sustained-responders was higher than that in nonresponders [odds ratio 2.3 (95% confidence interval 1.1–4.6); 16%vs 7.9%]. Multivariate analysis revealed that LMP7-K and HCV-RNA quantity were independent factors influencing the outcome of IFN therapy [4.5 (1.4–14); P=0.011, 0.40 (0.24–0.65); P=0.0003, respectively]. Furthermore, among patients with a low viral load (≤ 2.0 Meq/mL), the LMP7-K positive patients had an even higher ratio of sustained response compared to those without LMP7-K [5.9 (1.6–22); 82%vs 44%; P=0.0062]. These findings suggest that a single nucleotide polymorphism of LMP7 gene is one of the important host factors which independently influence the response to IFN in patients with chronic hepatitis C.