Premium
Association of TNF‐α genetic polymorphism with HLA DPB1 * 0301
Author(s) -
Kim S. H.,
Ye Y. M.,
Lee S. K.,
Choi J. H.,
Holloway J. W.,
Park C. S.,
Park H. S.
Publication year - 2006
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2006.02567.x
Subject(s) - single nucleotide polymorphism , genotyping , genotype , allele , human leukocyte antigen , atopy , immunology , genetics , polymorphism (computer science) , odds ratio , asthma , gene , biology , medicine , antigen
Summary 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.