Positional identification of an asthma susceptibility gene on human chromosome 5q33.
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.
Noguchi
Emiko
E
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
Yokouchi
Yukako
Y
Zhang
Jiang
J
Shibuya
Kazuko
K
Shibuya
Akira
A
Bannai
Makoto
M
Tokunaga
Katsushi
K
Doi
Hitomi
H
Tamari
Mayumi
M
Shimizu
Makiko
M
Shirakawa
Taro
T
Shibasaki
Masanao
M
Ichikawa
Kunio
K
Arinami
Tadao
T
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
D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human