Association of TNF-alpha genetic polymorphism with HLA DPB1*0301.
BACKGROUND
We speculated TNF-alpha can be one of candidate gene for aspirin-intolerant asthma (AIA) because TNF-alpha is pro-inflammatory cytokine and known to be increased level in asthmatic airways. In addition, genetic interaction between TNF-alpha and human antigen leucocyte (HLA) DPB1*0301, which is a strong genetic marker for AIA, was examined for its close location within chromosome 6.


METHODS
To investigate genetic association of TNF-alpha with an AIA phenotype, three study groups (163 patients with AIA, 197 patients with aspirin-tolerant asthma (ATA), 257 normal control subjects) were enrolled. Single nucleotide polymorphisms (SNPs) were genotyped using a single-base extension method and HLA DPB1 genotyping was determined by high-throughput sequencing method.


RESULTS
All five SNPs of TNF-alpha were tested; there were no significant differences in allele and genotype frequencies among the three groups. However, significant association between TNF-alpha-308G>A polymorphism and atopy status was noted (P<0.05). Gene to gene interaction between TNF-alpha-1031T>C (or -863C>A or -857C>A) and HLA DPB1*0301could synergistically increase the susceptibility to AIA with odds ratio (OR) to 7.738 (or OR=8.184 for -863C>A, OR=7.500 for -857C>T, P<0.001, respectively).


CONCLUSIONS
TNF-alpha promoter polymorphism may significantly increase susceptibility to AIA by gene-to-gene interaction with HLA DPB1*0301.
Kim
S-H
SH
Department of Allergy and Rheumatology, Ajou University School of Medicine, Suwon, Korea.
Ye
Y-M
YM
Lee
S-K
SK
Choi
J-H
JH
Holloway
J W
JW
Park
C-S
CS
Park
H-S
HS
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D001241:Aspirin / Q000009:adverse effects; D001249:Asthma / Q000139:chemically induced* / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D050172:Genes, X-Linked; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006682:HLA-DP Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005819:Genetic Markers; D006682:HLA-DP Antigens; D014409:Tumor Necrosis Factor-alpha; D001241:Aspirin