title: Association between TNFA polymorphism and the development of asthma in the Japanese population.
abstract: Tumor necrosis factor (TNF) is a proinflammatory cytokine that participates in the inflammatory reaction in patients with asthma. The TNFA and TNFB genes, which encode TNF-alpha and TNF-beta, respectively, are located within the region encoding the human major histocompatibility complex on chromosome 6p21.3, which showed linkage to atopic asthma in our genome-wide search. To determine whether polymorphisms in the 5' flanking region of the TNFA gene (-1031C/T, -863C/A, and -857C/T) and an NcoI polymorphism in the TNFB gene (LTA NcoI) are associated with the development of asthma, we performed transmission disequilibrium tests of families identified through children with atopic asthma. Genotypes of families were determined by polymerase chain reaction-based restriction fragment length polymorphism or SNaPshot analysis. Transmission disequilibrium tests of 144 asthmatic families revealed that transmission of the -857C allele and the -1031T-863C-857C haplotype in the TNFA gene to asthma-affected offspring occurred more frequently than expected (-857C allele, p = 0.0055; -1031T-863C-857C haplotype, p = 0.0002). Our results suggest that TNFA or nearby genes, including those in the major histocompatibility complex region, may contribute to the development of asthma in the Japanese population.
authors.affiliation: Department of Medical Genetics, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba City, Japan. mo00f210@md.tsukuba.ac.jp
authors.forename: Emiko
authors.initials: E
authors.lastname: Noguchi
authors.forename: Yukako
authors.initials: Y
authors.lastname: Yokouchi
authors.forename: Masanao
authors.initials: M
authors.lastname: Shibasaki
authors.forename: Michharu
authors.initials: M
authors.lastname: Inudou
authors.forename: Satoko
authors.initials: S
authors.lastname: Nakahara
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nogami
authors.forename: Masashi
authors.initials: M
authors.lastname: Kamioka
authors.forename: Kimiko
authors.initials: K
authors.lastname: Yamakawa-Kobayashi
authors.forename: Kunio
authors.initials: K
authors.lastname: Ichikawa
authors.forename: Akira
authors.initials: A
authors.lastname: Matsui
authors.forename: Tadao
authors.initials: T
authors.lastname: Arinami
mesh_terms: D001249:Asthma / Q000235:genetics*; D002648:Child; D002896:Chromosomes, Human, Pair 6; D006239:Haplotypes; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008233:Lymphotoxin-alpha / Q000235:genetics; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha