Human Molecular Genetics Advance Access originally published online on December 17, 2003
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Human Molecular Genetics, 2004, Vol. 13, No. 4 397-403
DOI: 10.1093/hmg/ddh036
Association of tumor necrosis factor polymorphisms with asthma and serum total IgE
1Department of Genetic Epidemiology, SNP Genetics Inc., 11th Floor, MaeHun B/D, 13 Chongro 4 Ga, Chongro-Gu, Seoul, 110-834 Korea, 2National Genome Information Center, Korea Research Institute of Bioscience and Biotechnology, 52 Eoeun-dong, Yuseong-gu, Daejeon, 305-333, Korea and 3Asthma Genome Research Group, Soonchunhyang University Hospital, Ajuo University Hospital, Ulsan University Hospital and Choong-Ang University Hospital, Korea
Received September 29, 2003; Revised November 25, 2003; Accepted December 3, 2003
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.
* To whom correspondence should be addressed at: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, 1174, Jung Dong, Wonmi Ku, Bucheon, Gyeonggi Do 420-021, Korea. Tel: +82 326215105; Fax: +82 326215023; Email: mdcspark{at}unitel.co.kr
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