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Satu Mäkelä, Jukka Mustonen, Ilpo Ala-Houhala, Mikko Hurme, Jukka Partanen, Olli Vapalahti, Antti Vaheri, Amos Pasternack, Human Leukocyte Antigen–B8-DR3 Is a More Important Risk Factor for Severe Puumala Hantavirus Infection than the Tumor Necrosis Factor–α(−308) G/A Polymorphism, The Journal of Infectious Diseases, Volume 186, Issue 6, 15 September 2002, Pages 843–846, https://doi.org/10.1086/342413
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Abstract
The tumor necrosis factor (TNF)–α(−308) G/A polymorphism (TNF-2) is in linkage disequilibrium with the human leukoctye antigen (HLA)–B8-DR3 haplotype. Both factors have been associated with severe Puumala hantavirus–induced nephropathia epidemica (NE). To examine which part of this extended haplotype might show the strongest association with the outcome of NE, the HLA-B, HLA-DRB1, and TNF-α(−308) alleles in 116 hospital-treated patients with NE were analyzed. The findings pointing to clinically severe NE were strongly associated with HLA-B8-DR3 haplotype. There was a trend toward severe disease in persons positive for TNF-2. This was probably due to strong linkage disequilibrium with HLA-B8-DR3, since there were no differences in the clinical severity of NE when TNF-2–positive/B8-DR3–negative persons were compared with TNF-2–negative/B8-DR3–negative persons. It is concluded that the HLA-B8-DR3 haplotype is an important contributor to the course of NE. The data indicate that the TNF-2 allele is not an independent risk factor for severe NE but a passive component in the extended haplotype