BACKGROUND: Genetic polymorphisms have been associated with asthma and asthma severity. OBJECTIVE: We sought to determine whether 3 polymorphisms were associated with severe asthma indicated either by the occurrence of a fatal (or near-fatal) asthma attack or by severe airflow obstruction. METHODS: We obtained DNA and clinical data from asthmatic subjects who either died or nearly died during an asthma attack and from a group of subjects with mild-to-moderate asthma who had never experienced a fatal or near-fatal asthma episode. These groups were compared with a group of nonatopic nonasthmatic control subjects. The level of airflow obstruction (FEV(1) percent predicted) in the subjects with mild-to-moderate asthma was used as an additional measure of disease severity. The subjects were genotyped for the IL4*C-589T promoter polymorphism and the IL4RA*Q576R and the FCERIB*E237G amino acid substitutions. RESULTS: The results showed that the FCERIB*E237G and IL4RA*Q576R polymorphisms were not associated with fatal or near-fatal asthma. However, the IL4*-589T allele was significantly increased in the subjects with fatal or near-fatal asthma compared with nonasthmatic subjects (odds ratio [OR], 1.8; P =.02) and subjects with mild-to-moderate asthma (OR, 1.9; P =.02). There was no interaction between the IL4*-589T and IL4RA*576R alleles. Of the 3 polymorphisms, only the IL4RA*576R allele was associated with severe airflow obstruction (OR, 8.2; P =.01). CONCLUSION: These data suggest that the IL4*-589T allele is a risk factor for life-threatening asthma and that the IL4RA*576R allele is a risk factor for a low level of lung function in asthmatic subjects.
BACKGROUND: Genetic polymorphisms have been associated with asthma and asthma severity. OBJECTIVE: We sought to determine whether 3 polymorphisms were associated with severe asthma indicated either by the occurrence of a fatal (or near-fatal) asthma attack or by severe airflow obstruction. METHODS: We obtained DNA and clinical data from asthmatic subjects who either died or nearly died during an asthma attack and from a group of subjects with mild-to-moderate asthma who had never experienced a fatal or near-fatal asthma episode. These groups were compared with a group of nonatopic nonasthmatic control subjects. The level of airflow obstruction (FEV(1) percent predicted) in the subjects with mild-to-moderate asthma was used as an additional measure of disease severity. The subjects were genotyped for the IL4*C-589T promoter polymorphism and the IL4RA*Q576R and the FCERIB*E237G amino acid substitutions. RESULTS: The results showed that the FCERIB*E237G and IL4RA*Q576R polymorphisms were not associated with fatal or near-fatal asthma. However, the IL4*-589T allele was significantly increased in the subjects with fatal or near-fatal asthma compared with nonasthmatic subjects (odds ratio [OR], 1.8; P =.02) and subjects with mild-to-moderate asthma (OR, 1.9; P =.02). There was no interaction between the IL4*-589T and IL4RA*576R alleles. Of the 3 polymorphisms, only the IL4RA*576R allele was associated with severe airflow obstruction (OR, 8.2; P =.01). CONCLUSION: These data suggest that the IL4*-589T allele is a risk factor for life-threatening asthma and that the IL4RA*576R allele is a risk factor for a low level of lung function in asthmatic subjects.
Authors: D Brassat; A A Motsinger; S J Caillier; H A Erlich; K Walker; L L Steiner; B A C Cree; L F Barcellos; M A Pericak-Vance; S Schmidt; S Gregory; S L Hauser; J L Haines; J R Oksenberg; M D Ritchie Journal: Genes Immun Date: 2006-04-20 Impact factor: 2.676
Authors: Fred D Finkelman; Simon P Hogan; Gurjit K Khurana Hershey; Marc E Rothenberg; Marsha Wills-Karp Journal: J Immunol Date: 2010-02-15 Impact factor: 5.422
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