BACKGROUND: Atopic disorders, including asthma, are very prevalent, affecting up to 40% of populations, and their incidence is on the rise. Although environmental factors are important in the development of atopy, there is a strong genetic predisposition. Several genes and chromosomal regions have been linked to atopy and asthma, supporting the polygenic nature of these disorders. IL-4 and IL-13 are T(H)2 cytokines with numerous activities that contribute to allergic inflammation and asthma. Both IL-4 and IL-13 use the IL-4 receptor alpha chain (IL-4Ralpha) as a component of their respective receptor systems. Allelic variants of IL-4Ralpha have been reported, and the R576IL-4Ralpha allele was recently shown to be a risk factor for atopy. OBJECTIVE: We sought to determine whether the R576 allele was associated with the prevalence or clinical severity of asthma. METHODS: We developed a rapid, reliable, PCR-based assay to screen individuals for the R576IL-4Ralpha allele and used this assay to genotype prospectively recruited individuals with asthma (n = 149) and control subjects (n = 57). RESULTS: There was a strong association of R576IL-4Ralpha with the prevalence and clinical severity of asthma. In a prospective cohort, homozygosity for R576 was significantly increased in individuals with asthma (n = 149, P =.03; relative risk 8.2) compared with controls (n = 57). Furthermore, 1 or 2 copies R576IL-4Ralpha correlated with asthma severity establishing a genotype-phenotype relationship and suggesting a gene dosage effect. CONCLUSIONS: Thus R576IL-4Ralpha acts as an allergic asthma susceptibility and disease-modifying gene and may serve as a clinically useful marker of asthma severity.
BACKGROUND:Atopic disorders, including asthma, are very prevalent, affecting up to 40% of populations, and their incidence is on the rise. Although environmental factors are important in the development of atopy, there is a strong genetic predisposition. Several genes and chromosomal regions have been linked to atopy and asthma, supporting the polygenic nature of these disorders. IL-4 and IL-13 are T(H)2 cytokines with numerous activities that contribute to allergic inflammation and asthma. Both IL-4 and IL-13 use the IL-4 receptor alpha chain (IL-4Ralpha) as a component of their respective receptor systems. Allelic variants of IL-4Ralpha have been reported, and the R576IL-4Ralpha allele was recently shown to be a risk factor for atopy. OBJECTIVE: We sought to determine whether the R576 allele was associated with the prevalence or clinical severity of asthma. METHODS: We developed a rapid, reliable, PCR-based assay to screen individuals for the R576IL-4Ralpha allele and used this assay to genotype prospectively recruited individuals with asthma (n = 149) and control subjects (n = 57). RESULTS: There was a strong association of R576IL-4Ralpha with the prevalence and clinical severity of asthma. In a prospective cohort, homozygosity for R576 was significantly increased in individuals with asthma (n = 149, P =.03; relative risk 8.2) compared with controls (n = 57). Furthermore, 1 or 2 copies R576IL-4Ralpha correlated with asthma severity establishing a genotype-phenotype relationship and suggesting a gene dosage effect. CONCLUSIONS: Thus R576IL-4Ralpha acts as an allergic asthma susceptibility and disease-modifying gene and may serve as a clinically useful marker of asthma severity.
Authors: Alex Soriano; Francisco Lozano; Harold Oliva; Felipe García; Meritxell Nomdedéu; Elisa De Lazzari; Carmen Rodríguez; Alicia Barrasa; José I Lorenzo; Jorge Del Romero; Montserrat Plana; José M Miró; José M Gatell; Jordi Vives; Teresa Gallart Journal: Immunogenetics Date: 2005-10-18 Impact factor: 2.846
Authors: Sally E Wenzel; Silvana Balzar; Elizabeth Ampleford; Gregory A Hawkins; William W Busse; William J Calhoun; Mario Castro; K Fan Chung; Serpil Erzurum; Benjamin Gaston; Elliot Israel; W Gerald Teague; Douglas Curran-Everett; Deborah A Meyers; Eugene R Bleecker Journal: Am J Respir Crit Care Med Date: 2006-12-14 Impact factor: 21.405
Authors: Peggy S Lai; Amir H Massoud; Mingcan Xia; Carter R Petty; Amparito Cunningham; Talal A Chatila; Wanda Phipatanakul Journal: J Allergy Clin Immunol Date: 2017-09-21 Impact factor: 10.793
Authors: Alan P Knutsen; Hari M Vijay; Barbara Kariuki; Luis A Santiago; Ralph Graff; Jonathan D Wofford; Maulik R Shah Journal: Clin Mol Allergy Date: 2010-03-18
Authors: Raffi Tachdjian; Clinton Mathias; Shadi Al Khatib; Paul J Bryce; Hong S Kim; Frank Blaeser; Brian D O'Connor; Danuta Rzymkiewicz; Andrew Chen; Michael J Holtzman; Gurjit K Hershey; Holger Garn; Hani Harb; Harald Renz; Hans C Oettgen; Talal A Chatila Journal: J Exp Med Date: 2009-09-21 Impact factor: 14.307