Association of TNF-α 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. Method 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(*)0301 could 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). Conclusion TNF-alpha promoter polymorphism may significantly increase susceptibility to AIA by gene-to-gene interaction with HLA DPB1(*)0301.