title: A single nucleotide polymorphism of the low molecular mass polypeptide 7 gene influences the interferon response in patients with chronic hepatitis C.
abstract: 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.
authors.affiliation: Department of Molecular Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: N
authors.initials: N
authors.lastname: Kuzushita
authors.forename: T
authors.initials: T
authors.lastname: Takehara
authors.forename: T
authors.initials: T
authors.lastname: Kanto
authors.forename: T
authors.initials: T
authors.lastname: Tatsumi
authors.forename: T
authors.initials: T
authors.lastname: Miyagi
authors.forename: M
authors.initials: M
authors.lastname: Jinushi
authors.forename: K
authors.initials: K
authors.lastname: Ohkawa
authors.forename: M
authors.initials: M
authors.lastname: Horimoto
authors.forename: A
authors.initials: A
authors.lastname: Kasahara
authors.forename: M
authors.initials: M
authors.lastname: Hori
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
authors.forename: N
authors.initials: N
authors.lastname: Hayashi
mesh_terms: 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
chemical_list: 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