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Association of TNF-alpha genetic polymorphism with HLA DPB1*0301.

Kim, SH; Ye, YM; Lee, SK; Choi, JH; Holloway, JW; Park, CS; Park, HS
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 36(10):1247-1253, 2006
Journal Title
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
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*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).

CONCLUSION: TNF-alpha promoter polymorphism may significantly increase susceptibility to AIA by gene-to-gene interaction with HLA DPB1*0301.
MeSH terms
AdultAnti-Inflammatory Agents, Non-Steroidal/adverse effectsAspirin/adverse effectsAsthma/chemically induced*Asthma/genetics*Asthma/immunologyCase-Control StudiesFemaleGene FrequencyGenes, X-LinkedGenetic MarkersGenetic Predisposition to DiseaseGenotypeHLA-DP Antigens/genetics*HLA-DP Antigens/immunologyHumansMaleMiddle AgedOdds RatioPolymorphism, Single Nucleotide*Tumor Necrosis Factor-alpha/genetics*Tumor Necrosis Factor-alpha/immunology
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
Journal Papers > Research Organization > Regional Clinical Trial Center
AJOU Authors
김, 승현예, 영민박, 해심
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