Background We speculated TNF-α can be one of candidate gene for aspirin-intolerant asthma (AIA) because TNF-α is pro-inflammatory cytokine and known to be increased level in asthmatic airways. In addition, genetic interaction between TNF-α 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-α 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-α were tested; there were no significant differences in allele and genotype frequencies among the three groups. However, significant association between TNF-α−308G>A polymorphism and atopy status was noted (P<0.05). Gene to gene interaction between TNF-α−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-α promoter polymorphism may significantly increase susceptibility to AIA by gene-to-gene interaction with HLA DPB1*0301.