Polymorphism of the tumor necrosis factor genes in patients with dermatitis herpetiformis.
In 18 patients with dermatitis herpetiformis (DH) of whom 16 were HLA-DR3 positive and 14 had the HLA-B8, -DR3 haplotype, the frequencies of known mutations of the tumor necrosis factor alpha (TNF-alpha) and TNF-beta genes were investigated using restriction fragment length polymorphism analysis and the single-strand conformational polymorphism technique. In DH, the phenotype frequency (28%) and allele frequency (0.58) of the rare TNF-beta allele TNFB*1 were significantly increased (normal control 12.4% and 0.37). For the TNF-alpha promoter/enhancer polymorphism, the rare allele TNF2 was more frequent in DH patients (11%, 0.47) compared to controls (2%, 0.16). Since functional studies have associated the rare TNFB*1 and TNF2 alleles with a higher secretion of TNF upon activation in vitro, the predominance of these two 'high-response' TNF alleles in DH patients may represent a genetic basis for the chronic inflammatory response in the skin and mucosal tissues of patients with DH.
Messer
G
G
Department of Dermatology, Ludwig-Maximilians-University, Munich, FRG.
Kick
G
G
Ranki
A
A
Koskimies
S
S
Reunala
T
T
Meurer
M
M
D000483:Alleles; D003874:Dermatitis Herpetiformis / Q000235:genetics* / Q000276:immunology; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D006680:HLA Antigens; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha