title: Interleukin-10 or tumor necrosis factor-alpha polymorphisms and the natural course of hepatitis C virus infection in a hyperendemic area of Japan.
abstract: We investigated the effects of polymorphisms in interleukin (IL)-10 and tumor necrosis factor (TNF)-alpha on the natural course of hepatitis C virus (HCV) infection in a community-based population in Japan. A total of 460 anti-HCV antibody seropositive individuals were classified into two groups, those who were positive or negative for HCV RNA. In HCV RNA-positive individuals with at least four annual alanine aminotransferase (ALT) measurements taken between 1993 and 2003, 74 exhibited persistently normal ALT levels, while 211 had one or more elevated ALT level tests. We examined the relationships between polymorphisms in the genes encoding IL-10 (-1082, -819, -592) or TNF-alpha (-308, -238) and HCV clearance, ALT abnormalities, or serum level of type IV collagen 7S, a marker of hepatic fibrosis. These polymorphisms were equally distributed among the patient subgroups with differential HCV RNA clearances or ALT abnormalities. Serum levels of type IV collagen 7S, however, were significantly higher in individuals with an A at position -238 or -308 in the TNF-alpha gene promoter than in individuals lacking these polymorphisms. We conclude that, while the relationships between inherited variations in IL-10 or TNF-alpha expression are not associated with alterations in HCV clearance or ALT levels, TNF-alpha polymorphisms may be associated with hepatic fibrosis.
authors.affiliation: Department of Internal Medicine II, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kusumoto
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Uto
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Hayashi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Takahama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakao
authors.forename: Robert
authors.initials: R
authors.lastname: Suruki
authors.forename: Sherri O
authors.initials: SO
authors.lastname: Stuver
authors.forename: Akio
authors.initials: A
authors.lastname: Ido
authors.forename: Hirohito
authors.initials: H
authors.lastname: Tsubouchi
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000483:Alleles; D024141:Collagen Type IV / Q000235:genetics; D004247:DNA / Q000378:metabolism; D005355:Fibrosis / Q000473:pathology; D006526:Hepatitis C / Q000235:genetics* / Q000821:virology*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D007564:Japan; D011110:Polymorphism, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D024141:Collagen Type IV; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D004247:DNA; D000410:Alanine Transaminase