Tumor Necrosis Factor-α 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)-α production can influence the severity of Hantavirus disease. We studied a TNF-α single-nucleotide promoter polymorphism (SNP) at position –238 (a guanine [G]-to-adenine [A] transition) and ex vivo TNF-α 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-α production. Creatinine levels correlated inversely with TNF-α production (R = –0.35, p < 0.05). The number of thrombocytes was significantly lower in patients with the GA-238 genotype (low TNF-α producers) compared with patients with the GG-238 genotype. In our study, genetically determined low production of TNF-α was associated with some parameters indicating a more severe clinical course of Puumala Hantavirus infection in humans, possibly by impaired activation of TNF-α-dependent antiviral mechanisms, which could in turn result in decreased clearance of Hantavirus.