Departments of Medical Genetics, Pediatrics, and Immunology, Graduate School of Comprehensive Human Sciences, University of Tsukuba; Department of Pediatrics, Tsukuba College of Technology; Tsukuba Medical Center Hospital, Tsukuba; Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Tokyo; and Laboratory of Genetics of Allergic Diseases, RIKEN SNP Research Center, Yokohama, Japan
Correspondence and requests for reprints should be addressed to Emiko Noguchi, M.D., Ph.D., Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki-ken, 305-8577, Japan. E-mail: enoguchi{at}md.tsukuba.ac.jp
Rationale: Asthma is a common respiratory disease with complexgenetic components. We previously reported strong evidence forlinkage between mite-sensitive asthma and markers on chromosome5q33. This area of linkage includes a region homologous to amouse area that contains a locus involved in regulation of airwayhyperreactivity. Objective: The aim of the present study isto identify asthma susceptibility genes on chromosome 5q33.Methods and Results: We performed mutation screening and associationanalyses of genes in the 9.4-Mb human linkage region. Transmissiondisequilibrium test analysis of 105 polymorphisms in 155 familieswith asthma revealed that six polymorphisms in cytoplasmic fragileX mental retardation protein (FMRP)–interacting protein2 gene were associated significantly with the development ofasthma (p = 0.000075; odds ratio, 5.9). These six polymorphismswere in complete linkage disequilibrium. In real-time quantitativepolymerase chain reaction analysis, subjects homozygous forthe haplotype overtransmitted to asthma-affected offspring showedsignificantly increased level of cytoplasmic FMRP interactingprotein 2 gene expression in lymphocytes compared with onesheterozygous for the haplotype (p = 0.038). Conclusions: Ourdata suggest that cytoplasmic FMRP interacting protein 2 areassociated with the development of atopic asthma in humans,and that targeting cytoplasmic FMRP interacting protein 2 couldbe a novel strategy for treating atopic asthma.
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Thorax,
February 1, 2010;
65(2):
124 - 131.
[Abstract][Full Text][PDF]
D. S. Postma and G. H. Koppelman Genetics of Asthma: Where Are We and Where Do We Go?
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May 1, 2009;
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283 - 287.
[Abstract][Full Text][PDF]
G. H. Koppelman, G. J. te Meerman, and D. S. Postma Genetic testing for asthma
Eur. Respir. J.,
September 1, 2008;
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775 - 782.
[Abstract][Full Text][PDF]
C. P. Hersh, B. A. Raby, M. E. Soto-Quiros, A. J. Murphy, L. Avila, J. Lasky-Su, J. S. Sylvia, B. J. Klanderman, C. Lange, S. T. Weiss, et al. Comprehensive Testing of Positionally Cloned Asthma Genes in Two Populations
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November 1, 2007;
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849 - 857.
[Abstract][Full Text][PDF]
A. M. Singh, P. E. Moore, J. E. Gern, R. F. Lemanske Jr., and T. V. Hartert Bronchiolitis to Asthma: A Review and Call for Studies of Gene-Virus Interactions in Asthma Causation
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January 15, 2007;
175(2):
108 - 119.
[Abstract][Full Text][PDF]
K. C. Barnes, A. V. Grant, N. N. Hansel, P. Gao, and G. M. Dunston African Americans with Asthma: Genetic Insights
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January 1, 2007;
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58 - 68.
[Abstract][Full Text][PDF]
C Brasch-Andersen, Q Tan, A D Borglum, A Haagerup, T R Larsen, J Vestbo, and T A Kruse Significant linkage to chromosome 12q24.32-q24.33 and identification of SFRS8 as a possible asthma susceptibility gene
Thorax,
October 1, 2006;
61(10):
874 - 879.
[Abstract][Full Text][PDF]
S. E. Wenzel and R. Covar Update in asthma 2005.
Am. J. Respir. Crit. Care Med.,
April 1, 2006;
173(7):
698 - 706.
[Full Text][PDF]
