Positional identification of an asthma susceptibility gene on human chromosome 5q33

Am J Respir Crit Care Med. 2005 Jul 15;172(2):183-8. doi: 10.1164/rccm.200409-1223OC. Epub 2005 May 5.


Rationale: 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.

Methods and 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.

Publication types

  • Comparative Study

MeSH terms

  • Asians / genetics*
  • Asthma / genetics*
  • Child
  • Chromosome Mapping
  • Chromosomes, Human, Pair 5*
  • Computer Systems
  • Cytoplasm / metabolism
  • DNA Mutational Analysis
  • Fragile X Mental Retardation Protein
  • Genetic Predisposition to Disease*
  • Haplotypes
  • Heterozygote
  • Homozygote
  • Humans
  • Linkage Disequilibrium
  • Lymphocytes / metabolism
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism


  • FMR1 protein, human
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Fragile X Mental Retardation Protein