Polymorphisms in the interleukin-4 and interleukin-4 receptor α chain genes confer susceptibility to asthma and atopy in a Caucasian population

• Published in: Clinical and experimental allergy Vol. 33; no. 8; pp. 1111 - 1117
• Main Authors: Beghé, B., Barton, S., Rorke, S., Peng, Q., Sayers, I., Gaunt, T., Keith, T. P., Clough, J. B., Holgate, S. T., Holloway, J. W.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.08.2003; Blackwell; Wiley Subscription Services, Inc
• Subjects: Adolescent; Adult; Allergic diseases; asthma; Asthma - genetics; Asthma - immunology; Biological and medical sciences; bronchial hyperresponsiveness; Case-Control Studies; Child; Child, Preschool; cytokines; Female; Gene Frequency; genes; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Hypersensitivity, Immediate - genetics; Hypersensitivity, Immediate - immunology; Immunopathology; Interleukin 4 receptor^a; Interleukin-4 - genetics; Linkage Disequilibrium; Male; Medical sciences; Phenotype; Polymorphism, Genetic; polymorphisms; Receptors, Interleukin-4 - genetics; Respiratory and ent allergic diseases; Statistics as Topic; Human; Immunopathology; Allergy; Hyperreactivity; Respiratory disease; genes; Cytokine; Bronchus; Genetic determinism; Epidemiology; polymorphisms; Asthma; Interleukin 4; Gene; Genetics; cytokines; Obstructive pulmonary disease; bronchial hyperresponsiveness; Polymorphism
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1046/j.1365-2222.2003.01731.x

Summary Background  IL‐4 by binding to its receptor (IL‐4R) is essential for the development of airway inflammation present in asthma, through the induction of IgE synthesis in B cells and differentiation of T cells to a Th2 phenotype. Objective  To investigate the role of four common polymorphisms in the IL‐4 (IL4‐34CT and IL4‐589CT) and IL‐4Rα chain (IL4RAI50V and IL4RAQ576R) genes in conferring susceptibility to the development of atopy and/or asthma. Methods  Two polymorphisms in the IL‐4 gene promoter, IL4‐34CT and IL4‐589CT, and two polymorphisms in the IL‐4Rα chain gene, IL4RAI50V and IL4RAQ576R, have been genotyped using PCR‐based methods in 341 asthmatic families and in 184 non‐asthmatic adults recruited from the south of England. Results  Case–control analysis did not reveal differences in the distribution of the four polymorphisms between asthmatics and controls. However, the transmission disequilibrium test showed that the IL4‐589 T allele was preferentially transmitted to asthmatic children (P=0.036) and that the IL4RAQ576 was preferentially transmitted to children with atopic asthma (P=0.018). Haplotype analysis showed a strong association between the IL4‐34T/‐589T haplotype and asthma per se (P=0.041), and a strong association between the IL4RA I50/Q576 haplotype and atopic asthma (P=0.006). Conclusion  Our data suggest that polymorphisms in the IL‐4 and IL‐4Rα chain genes might play a role both conferring susceptibility to and modulating severity of atopy and asthma.