Association of polymorphisms in CASP10 and CASP8 with FEV1/FVC and bronchial hyperresponsiveness in ethnically diverse asthmatics
Article first published online: 24 SEP 2008
© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd
Clinical & Experimental Allergy
Volume 38, Issue 11, pages 1738–1744, November 2008
How to Cite
Smith, A. K., Lange, L. A., Ampleford, E. J., Meyers, D. A., Bleecker, E. R. and Howard, T. D. (2008), Association of polymorphisms in CASP10 and CASP8 with FEV1/FVC and bronchial hyperresponsiveness in ethnically diverse asthmatics. Clinical & Experimental Allergy, 38: 1738–1744. doi: 10.1111/j.1365-2222.2008.03095.x
- Issue published online: 22 OCT 2008
- Article first published online: 24 SEP 2008
- Submitted 29 August 2007; revised 23 June 2008; accepted 30 June 2008
- bronchial hyperresponsiveness;
- chromosome 2q;
Background Several chromosomal regions have been identified using family-based linkage analysis to contain genes contributing to the development of asthma and allergic disorders. One of these regions, chromosome 2q32-q33, contains a gene cluster containing CFLAR, CASP10 and CASP8. These genes regulate the extrinsic apoptosis pathway utilized by several types of immune and structural cells that have been implicated in the pathogenesis of asthma.
Objective To assess the role of genetic variation in CFLAR, CASP10 and CASP8 in asthma and related phenotypes in individuals of diverse ethnic backgrounds.
Methods We tested 26 single nucleotide polymorphisms (SNPs) in the CFLAR, CASP10 and CASP8 gene cluster for association with asthma and related phenotypes in African-American, non-Hispanic whites, and Hispanic case–control populations (cases, N=517, controls, N=644).
Results Five CASP10 SNPS were associated with forced expiratory volume in 1 s (FEV1)/forced expiration volume capacity (FVC) in the African-American subjects with asthma (P=0.0009–0.047). Nine SNPs, seven in CASP10 and two in CASP8, were also associated with the degree of bronchial hyperresponsiveness (BHR) (as determined by PC20) in race-specific analysis, predominately in the Non-Hispanic white cases. Two SNPs, rs6750157 in CASP10 and rs1045485 in CASP8 were modestly associated with asthma in the African-American (P=0.025) and Hispanic (P=0.033) populations, respectively.
Conclusion These data suggest a role for CASP10 as a potential modifier of the asthma phenotype, specifically with measures of airway obstruction and BHR.