title: A TLR2 polymorphism is associated with type 1 diabetes and allergic asthma.
abstract: Type 1 diabetes (T1D) and allergic asthma are immune-mediated diseases. Pattern recognition receptors are proteins expressed by cells in the immune system to identify microbial pathogens and endogenous ligands. Toll-like receptors (TLRs) and CD14 are members of this family and could represent a molecular link between microbial infections and immune-mediated diseases. Diverging hypotheses regarding whether there exists a common or inverse genetic etiology behind these immune-mediated diseases have been presented. We aimed to test whether there exist common or inverse associations between polymorphisms in the pattern recognition receptors TLR2, TLR4 and CD14 and T1D and allergic asthma. Eighteen single nucleotide polymorphisms (SNPs) were genotyped in TLR2 (2), TLR4 (12) and CD14 (4) in 700 T1D children, 357 nuclear families with T1D children and 796 children from the 'Environment and Childhood Asthma' study. Allele and haplotype frequencies were analyzed in relation to diseases and in addition transmission disequilibrium test analyses were performed in the family material. Both T1D and allergic asthma were significantly associated with the TLR2 rs3804100 T allele and further associated with the haplotype including this SNP, possibly representing a susceptibility locus common for the two diseases. Neither TLR4 nor CD14 were associated with T1D or allergic asthma.
authors.affiliation: Institute of Medical Genetics, Faculty Division Ullevål University Hospital, University of Oslo, Blindern, Norway. marit.bjornvold@medisin.uio.no
authors.forename: M
authors.initials: M
authors.lastname: Bjørnvold
authors.forename: M C
authors.initials: MC
authors.lastname: Munthe-Kaas
authors.forename: T
authors.initials: T
authors.lastname: Egeland
authors.forename: G
authors.initials: G
authors.lastname: Joner
authors.forename: K
authors.initials: K
authors.lastname: Dahl-Jørgensen
authors.forename: P R
authors.initials: PR
authors.lastname: Njølstad
authors.forename: H E
authors.initials: HE
authors.lastname: Akselsen
authors.forename: K
authors.initials: K
authors.lastname: Gervin
authors.forename: K C L
authors.initials: KC
authors.lastname: Carlsen
authors.forename: K H
authors.initials: KH
authors.lastname: Carlsen
authors.forename: D E
authors.initials: DE
authors.lastname: Undlien
mesh_terms: D000293:Adolescent; D000483:Alleles; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology; D008297:Male; D009664:Norway; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics* / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology
chemical_list: D018950:Lipopolysaccharide Receptors; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4