Human leukocyte antigen-B8-DR3 is a more important risk factor for severe Puumala hantavirus infection than the tumor necrosis factor-alpha(-308) G/A polymorphism.
The tumor necrosis factor (TNF)-alpha(-308) G/A polymorphism (TNF-2) is in linkage disequilibrium with the human leukocyte 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-alpha(-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.
Mäkelä
Satu
S
Medical School, University of Tampere and Tampere University Hospital, Tampere, Tampere, Finland. satu.marjo.makela@uta.fi
Mustonen
Jukka
J
Ala-Houhala
Ilpo
I
Hurme
Mikko
M
Partanen
Jukka
J
Vapalahti
Olli
O
Vaheri
Antti
A
Pasternack
Amos
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D015795:HLA-B8 Antigen / Q000235:genetics*; D015803:HLA-DR3 Antigen / Q000235:genetics*; D006239:Haplotypes; D006480:Hemorrhagic Fever with Renal Syndrome / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D029262:Puumala virus / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D015795:HLA-B8 Antigen; D015803:HLA-DR3 Antigen; D014409:Tumor Necrosis Factor-alpha