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Tumor necrosis factors (TNF; TNFA and TNFB) are major pro-inflammatory cytokines that are thought to be important in the pathogenesis of asthma. However, the functions of genetic polymorphisms in these cytokines have not been thoroughly examined in the context of asthma pathology. In an effort to discover polymorphism(s) in genes whose variant(s) have been implicated in asthma phenotypes, we examined the genetic effects of  TNF  ( TNFA  and  TNFB ) polymorphisms on asthma and total serum IgE level. Seven common single-nucleotide polymorphisms (SNP) in TNF genes were genotyped in a Korean asthma cohort (asthmatics  n =550, normal controls  n =171). Six common haplotypes could be constructed in the  TNF  gene cluster due to very strong LD between  TNFA  and  TNFB , located 13 kb apart on chromosome 6p21. One SNP ( TNFA-308G &gt; A ) showed a significant association with the risk of asthma ( P =0.0004). The frequency of  TNFA-308A  allele-containing genotype in asthmatics (9.8%) was much lower than that in normal controls (22.9%). The protective effects of this polymorphism on asthma were also evident in separated subgroups by atopic status ( P =0.05 in non-atopic subjects and  P =0.003 in atopic subjects). The most common haplotype of the  TNF  gene ( TNF-ht1[GGTCCGG] ) was associated with total serum IgE (immunoglobulin E) levels in asthma patients, especially in non-atopic patients ( P =0.004). Genetic variants of  TNF  might be involved in development of asthma and total serum IgE level in bronchial asthma patients. The results of this study could be helpful to understand the function of important  TNF  genes in asthma and IgE production.

Association of tumor necrosis factor polymorphisms with asthma and serum total IgE