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Association between TNFA Polymorphism and the Development of Asthma in the Japanese Population

Department of Medical Genetics, Institute of Basic Medical Sciences and Department of Pediatrics, Institute of Clinical Medicine, University of Tsukuba, Tsukuba City; Kensei General Hospital, Nishiibaraki-gun; and Nogami Children's Clinic, Ryugasaki City, Ibaraki-ken, Japan

Correspondence and requests for reprints should be addressed to Emiko Noguchi, M.D., Ph.D., Department of Medical Genetics, Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki-ken, 305-8575, Japan. E-mail: mo00f210{at}md.tsukuba.ac.jp

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- and TNF-ß, 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.

Key Words: genetics • haplotype • transmission disequilibrium test

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