07a0d4ae-5a6f-4899-9672-43fa38f05bad
title
Association of tumor necrosis factor polymorphisms with asthma and serum total  IgE .
81e6a7ca-06e1-4c0a-b247-72e845628d7c
abstract
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>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.