title: NOD1 variation, immunoglobulin E and asthma.
abstract: 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 (ND(1)+32656) near the beginning of intron IX that accounted for approximately 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 ND(1)+32656 alleles was observed to a protein from nuclei of the Calu 3 epithelial cell line. In an accompanying study, the deletion allele (ND(1)+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.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: Pirro
authors.initials: P
authors.lastname: Hysi
authors.forename: Michael
authors.initials: M
authors.lastname: Kabesch
authors.forename: Miriam F
authors.initials: MF
authors.lastname: Moffatt
authors.forename: Michaela
authors.initials: M
authors.lastname: Schedel
authors.forename: David
authors.initials: D
authors.lastname: Carr
authors.forename: Youming
authors.initials: Y
authors.lastname: Zhang
authors.forename: Brenda
authors.initials: B
authors.lastname: Boardman
authors.forename: Erika
authors.initials: E
authors.lastname: von Mutius
authors.forename: Stephan K
authors.initials: SK
authors.lastname: Weiland
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Leupold
authors.forename: Christian
authors.initials: C
authors.lastname: Fritzsch
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.forename: A William
authors.initials: AW
authors.lastname: Musk
authors.forename: Alan
authors.initials: A
authors.lastname: James
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nunez
authors.forename: Naohiro
authors.initials: N
authors.lastname: Inohara
authors.forename: William O C
authors.initials: WO
authors.lastname: Cookson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000483:Alleles; D017398:Alternative Splicing; D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D002460:Cell Line; D002648:Child; D002897:Chromosomes, Human, Pair 7; D004848:Epithelium / Q000378:metabolism; D017353:Gene Deletion; D005821:Genetic Techniques; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000737:chemistry / Q000235:genetics*; D007249:Inflammation; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D007438:Introns; D008957:Models, Genetic; D053474:Nod1 Signaling Adaptor Protein; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary; D014018:Tissue Distribution
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; D007073:Immunoglobulin E