Human Molecular Genetics Advance Access published online on December 17, 2003
Human Molecular Genetics, doi:10.1093/hmg/ddh036
© 2003 by Oxford University Press
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1 Department of Genetic Epidemiology, SNP Genetics, Inc., 11th Floor, MaeHun B/D, 13 Chongro 4 Ga, Chongro-Gu, Seoul, Korea 110-834
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 13kb 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.
Article
Association of Tumor Necrosis Factor (TNF) Polymorphisms With Asthma and Serum Total IgE
2 National Genome Information Center, Korea Research Institute of Bioscience & Biotechnology, 52 Eoeun-dong, Yuseong-gu, Daejeon, Korea 305-333
3 Asthma Genome Research Group, Soonchunhyang University Hospital, Ajuo University Hospital, Ulsan University Hospital and Choong-Ang University Hospital
4 Asthma Genome Research Group, Soonchunhyang University Hospital, Ajuo University Hospital, Ulsan University Hospital and Choong-Ang University Hospital; Division of Allergy and Respiratory
Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, 1174, Jung Dong, Wonmi Ku, Bucheon, Gyeonggi Do, Korea 420-021
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