Polymorphisms in interleukin-1 receptor-associated kinase 4 are associated with total serum IgE

• Published in: Allergy Vol. 64; no. 5; pp. 746 - 753
• Main Authors: Tewfik, M.A, Bossé, Y, Lemire, M, Hudson, T.J, Vallée-Smejda, S, Al-Shemari, H, Laprise, C, Desrosiers, M
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.05.2009; Blackwell Publishing Ltd; Blackwell
• Subjects: Adult; Allergies; asthma; Biological and medical sciences; Chronic Disease; Chronic obstructive pulmonary disease, asthma; chronic rhinosinusitis; Cross-Sectional Studies; Cytokines; Dermatology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Frequency - genetics; Gene Frequency - immunology; genetics innate immunity; Genotype; Genotype & phenotype; Humans; Hypersensitivity - genetics; Hypersensitivity - immunology; Immune system; immunoglobulin E; Immunoglobulin E - blood; Immunoglobulins; Interleukin-1 Receptor-Associated Kinases - genetics; Interleukin-1 Receptor-Associated Kinases - immunology; Linkage Disequilibrium; Male; Medical sciences; Middle Aged; Pneumology; Polymorphism; Polymorphism, Single Nucleotide; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Surveys and Questionnaires; Nose disease; Genetic variability; Rhinitis; IgE; Natural immunity; Sinusitis; Association; Immunology; ENT disease; Bronchus disease; Genetics; Serum; genetics innate immunity; Obstructive pulmonary disease; Interleukin 1 receptor; Lung disease; Immunopathology; Enzyme; Respiratory disease; Dermatology; Transferases; Genotype; immunoglobulin E; Asthma; Chronic; Kinase; chronic rhinosinusitis; Paranasal sinus disease; Polymorphism
• ISSN: 0105-4538; 1398-9995; 0108-1675
• DOI: 10.1111/j.1398-9995.2008.01889.x

Serum immunoglobulin E (IgE) level is recognized to be under strong genetic control, but the causal and susceptibility genes remain to be identified. We sought to investigate the association between single nucleotide polymorphisms (SNPs) in the Toll-like receptor (TLR) signaling pathway and total serum IgE level. A population of 206 patients with severe chronic rhinosinusitis (CRS) was used. Precise phenotyping of patients was accomplished by means of a questionnaire and clinical examination. Blood was drawn for measurement of total serum IgE, as well as DNA extraction. A maximally informative set of SNPs in the TLR1, 2, 3, 4, 6, 9, 10, CD14, MD2, MyD88, IRAK4, and TRAF6 genes were selected and genotyped. Significant findings were replicated in a second independent population of 956 subjects from 227 families with asthma. A total of 97 out of 104 SNPs were successfully genotyped. Three SNPs in IRAK4- rs1461567, rs4251513, and rs4251559 - were associated with total serum IgE levels (P < 0.004). In the replication sample, the same SNPs as well as the same orientation of the risk allele were associated with IgE levels (P < 0.031). These results demonstrate a clear association between polymorphisms in the IRAK4 gene and serum IgE levels in patients with CRS and asthma. IRAK4 may be important in the regulation of IgE levels in patients with inflammatory diseases of the airways.