title: Tumor necrosis factor-alpha genetic polymorphism may contribute to progression of bovine leukemia virus-infection.
abstract: In a previous report, we had indicated that in a sheep model, the expression of tumor necrosis factor (TNF)-alpha was closely associated with disease progression in sheep experimentally infected with bovine leukemia virus (BLV). However, individual variabilities are observed in these responses in BLV-infected animals. To attempt to identify genetic factors promoting the progression to BLV-induced lymphoma, we endeavored to determine whether there are any polymorphisms in the TNF-alpha gene among 291 individuals and whether this would affect the level of TNF-alpha expression and concomitant progression of BLV-induced disease or increase in the provirus load in the carriers. We found that the frequency of the TNF-alpha -824G allele, which has been associated with low transcription activity of the promoter/predicted enhancer region of the bovine TNF-alpha gene, was higher in individuals with BLV-induced lymphoma than in asymptomatic carrier individuals. In addition, we observed a tendency for increased BLV-provirus load in cattle with TNF-alpha -824G/G homozygote compared to TNF-alpha -824A/A homozygote or TNF-alpha -824A/G. These data suggest that the observed polymorphism in the promoter region of TNF-alpha gene could at least in part contribute to the progression of lymphoma in BLV-infection.
authors.affiliation: Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan. konnai@vetmed.kokudai.ac.jp
authors.forename: Satoru
authors.initials: S
authors.lastname: Konnai
authors.forename: Tatsufumi
authors.initials: T
authors.lastname: Usui
authors.forename: Manabu
authors.initials: M
authors.lastname: Ikeda
authors.forename: Junko
authors.initials: J
authors.lastname: Kohara
authors.forename: Toh-ichi
authors.initials: T
authors.lastname: Hirata
authors.forename: Kosuke
authors.initials: K
authors.lastname: Okada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ohashi
authors.forename: Misao
authors.initials: M
authors.lastname: Onuma
mesh_terms: D000818:Animals; D001483:Base Sequence; D002353:Carrier State / Q000821:virology; D002417:Cattle; D002460:Cell Line; D018450:Disease Progression; D016583:Enzootic Bovine Leukosis / Q000235:genetics* / Q000276:immunology / Q000821:virology; D015870:Gene Expression; D005787:Gene Frequency; D001909:Leukemia Virus, Bovine; D008223:Lymphoma / Q000235:genetics / Q000662:veterinary* / Q000821:virology; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011533:Proviruses; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology; D019562:Viral Load
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha