title: Positional identification of an asthma susceptibility gene on human chromosome 5q33.
abstract: BACKGROUND
  Asthma is a common respiratory disease with complex genetic components. We previously reported strong evidence for linkage between mite-sensitive asthma and markers on chromosome 5q33. This area of linkage includes a region homologous to a mouse area that contains a locus involved in regulation of airway hyperreactivity.
  
  
  OBJECTIVE
  The aim of the present study is to identify asthma susceptibility genes on chromosome 5q33.
  
  
  RESULTS
  We performed mutation screening and association analyses of genes in the 9.4-Mb human linkage region. Transmission disequilibrium test analysis of 105 polymorphisms in 155 families with asthma revealed that six polymorphisms in cytoplasmic fragile X mental retardation protein (FMRP)-interacting protein 2 gene were associated significantly with the development of asthma (p = 0.000075; odds ratio, 5.9). These six polymorphisms were in complete linkage disequilibrium. In real-time quantitative polymerase chain reaction analysis, subjects homozygous for the haplotype overtransmitted to asthma-affected offspring showed significantly increased level of cytoplasmic FMRP interacting protein 2 gene expression in lymphocytes compared with ones heterozygous for the haplotype (p = 0.038).
  
  
  CONCLUSIONS
  Our data suggest that cytoplasmic FMRP interacting protein 2 are associated with the development of atopic asthma in humans, and that targeting cytoplasmic FMRP interacting protein 2 could be a novel strategy for treating atopic asthma.
authors.affiliation: Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki-ken, 305-8577, Japan. enoguchi@md.tsukuba.ac.jp
authors.forename: Emiko
authors.initials: E
authors.lastname: Noguchi
authors.forename: Yukako
authors.initials: Y
authors.lastname: Yokouchi
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhang
authors.forename: Kazuko
authors.initials: K
authors.lastname: Shibuya
authors.forename: Akira
authors.initials: A
authors.lastname: Shibuya
authors.forename: Makoto
authors.initials: M
authors.lastname: Bannai
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Hitomi
authors.initials: H
authors.lastname: Doi
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tamari
authors.forename: Makiko
authors.initials: M
authors.lastname: Shimizu
authors.forename: Taro
authors.initials: T
authors.lastname: Shirakawa
authors.forename: Masanao
authors.initials: M
authors.lastname: Shibasaki
authors.forename: Kunio
authors.initials: K
authors.lastname: Ichikawa
authors.forename: Tadao
authors.initials: T
authors.lastname: Arinami
mesh_terms: D044466:Asian People / Q000235:genetics*; D001249:Asthma / Q000235:genetics*; D002648:Child; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D003199:Computer Systems; D003593:Cytoplasm / Q000378:metabolism; D004252:DNA Mutational Analysis; D051860:Fragile X Messenger Ribonucleoprotein 1; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008214:Lymphocytes / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human