A single nucleotide polymorphism of the low molecular mass polypeptide 7 gene influences the interferon response in patients with chronic hepatitis C.
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 (< or = 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.
Sugimoto
Y
Y
Department of Molecular Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Kuzushita
N
N
Takehara
T
T
Kanto
T
T
Tatsumi
T
T
Miyagi
T
T
Jinushi
M
M
Ohkawa
K
K
Horimoto
M
M
Kasahara
A
A
Hori
M
M
Sasaki
Y
Y
Hayashi
N
N
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D003546:Cysteine Endopeptidases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D006801:Humans; D034982:Integration Host Factors; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D009097:Multienzyme Complexes; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D046988:Proteasome Endopeptidase Complex; D016896:Treatment Outcome; D019562:Viral Load
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D034982:Integration Host Factors; D016898:Interferon-alpha; D009097:Multienzyme Complexes; C071692:TAP2 protein, human; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex