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Hysi, P.* ; Kabesch, M.* ; Moffatt, M.F.* ; Schedel, M.* ; Carr, D.* ; Zhang, Y.* ; Boardman, B.* ; von Mutius, E.* ; Weiland, S.K.* ; Leupold, W.* ; Fritzsch, C.* ; Klopp, N. ; Musk, A.W.* ; James, A.* ; Nunez, G.* ; Inohara, N.* ; Cookson, W.O.*

NOD1 variation, immunoglobulin E and asthma.

Hum. Mol. Genet. 14, 935-941 (2005)
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Asthma is a familial inflammatory disease of the airways of the lung. Microbial exposures in childhood protect against asthma through unknown mechanisms. The innate immune system is able to identify microbial components through a variety of pattern-recognition receptors (PRRs). NOD1 is an intracellular PRR that initiates inflammation in response to bacterial diaminopimelic acid (iE-DAP). The NOD1 gene is on chromosome 7p14, in a region that has been genetically linked to asthma. We carried out a systematic search for polymorphism in the gene. We found an insertion-deletion polymorphism (ND1+32656) near the beginning of intron IX that accounted for similar to 7% of the variation in IgE in two panels of families (P < 0.0005 in each). Allele*2 (the insertion) was associated with high IgE levels. The same allele was strongly associated with asthma in an independent study of 600 asthmatic children and 1194 super-normal controls [odds ratio (OR) 6.3; 95% confidence interval (CI) 1.4-28.3, dominant model]. Differential binding of the two ND1+32656 alleles was observed to a protein from nuclei of the Calu 3 epithelial cell line. In an accompanying study, the deletion allele (ND1+32656*1) was found to be associated with inflammatory bowel disease. The results indicate that intracellular recognition of specific bacterial products affects the presence of childhood asthma.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter QUANTITATIVE TRAITS; FOUNDER POPULATION; CROHNS-DISEASE; ASSOCIATION; GENE; SUSCEPTIBILITY; POLYMORPHISMS; LOCUS; IGE; RESPONSIVENESS
Sprache englisch
Veröffentlichungsjahr 2005
HGF-Berichtsjahr 2005
ISSN (print) / ISBN 0964-6906
e-ISSN 1460-2083
Zeitschrift Human Molecular Genetics
Quellenangaben Band: 14, Heft: 7, Seiten: 935-941 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
POF Topic(s) 30503 - Chronic Diseases of the Lung and Allergies
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-503900-003
PubMed ID 15718249
DOI 10.1093/hmg/ddi087
WOS ID WOS:000227975800006
Scopus ID 20244364812
Erfassungsdatum 2005-10-17
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