title: Tumor necrosis factor-alpha genetic predisposing factors can influence clinical severity in nephropathia epidemica.
abstract: Severe human infection with Hantavirus is characterized by high fever, cold chills, thrombocytopenia, arterial hypotension, acute renal failure, and/or adult respiratory distress syndrome (ARDS)-like pulmonary involvement, but the clinical course varies greatly between individuals. We investigated whether genetically determined differences in tumor necrosis factor (TNF)-alpha production can influence the severity of Hantavirus disease. We studied a TNF-alpha single-nucleotide promoter polymorphism (SNP) at position -238 (a guanine [G]-to-adenine [A] transition) and ex vivo TNF-alpha production in a recall study of 36 Belgian patients who had a serologically proven form of Puumala virus-induced Hantavirus infection with the kidney as main target organ. In our study, the highest creatinine levels were found in patients with the lowest ex vivo TNF-alpha production. Creatinine levels correlated inversely with TNF-alpha production (R = -0.35, p < 0.05). The number of thrombocytes was significantly lower in patients with the GA-238 genotype (low TNF-alpha producers) compared with patients with the GG-238 genotype. In our study, genetically determined low production of TNF-alpha was associated with some parameters indicating a more severe clinical course of Puumala Hantavirus infection in humans, possibly by impaired activation of TNF-alpha-dependent antiviral mechanisms, which could in turn result in decreased clearance of Hantavirus.
authors.affiliation: Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
authors.forename: Piet
authors.initials: P
authors.lastname: Maes
authors.forename: Jan
authors.initials: J
authors.lastname: Clement
authors.forename: Paul H P
authors.initials: PH
authors.lastname: Groeneveld
authors.forename: Paul
authors.initials: P
authors.lastname: Colson
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: Marc
authors.initials: M
authors.lastname: Van Ranst
mesh_terms: D020022:Genetic Predisposition to Disease; D006480:Hemorrhagic Fever with Renal Syndrome / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D029262:Puumala virus; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha