Association of TNF-alpha promoter polymorphisms with aspirin-induced urticaria.
OBJECTIVE
Although the pathogenesis of aspirin-induced urticaria (AIU) is not fully understood, mast cell activation has been noted in patients with AIU. Tumour necrosis factor (TNF)-alpha, a potent pro-inflammatory cytokine, is released by human skin mast cells and other inflammatory cells in patients with urticaria. To investigate the role of TNF-alpha promoter polymorphisms in the development of AIU, we performed an association study of TNF-alpha promoter polymorphisms with AIU phenotype.


METHODS
Two hundred thirty-nine patients with AIU consisting of 120 patients with aspirin intolerant chronic urticaria (AICU) and 119 with aspirin-intolerant acute urticaria (AIAU), and 524 normal controls were enrolled. AIU was confirmed by oral aspirin challenge test. Five SNPs in the TNF-alpha gene (-1031T>C, -863C>A, -857C>T, -308G>A, -238G>A) were genotyped by a single-base extension method. Haplotype analyses were done.


RESULTS
The genotype frequencies of TNF-1031T>C and TNF-863C>A were significantly higher in the AIU patients than in the normal controls in both co-dominant (P = 0.014, P = 0.007) and dominant (P = 0.007, P = 0.004) models. The frequency of TNF-ht2[CACGG] containing a genotype in the AIU group was significantly higher in the normal controls with both co-dominant (P = 0.004, Pc = 0.02) and dominant models (P = 0.002, Pc = 0.01).


CONCLUSIONS
These findings suggest that the two promoter polymorphisms of TNF-alpha at -1031T>C and -863C>A may contribute to the development of AIU.
Choi
J H
JH
Department of Internal Medicine, Hallym University College of Medicine, Seoul, Korea.
Kim
S H
SH
Cho
B Y
BY
Lee
S K
SK
Kim
S H
SH
Suh
C H
CH
Park
H S
HS
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007723:Korea / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012882:Skin Tests; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014581:Urticaria / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014409:Tumor Necrosis Factor-alpha; D001241:Aspirin