Association of polymorphisms in CASP10 and CASP8 with FEV(1)/FVC and bronchial hyperresponsiveness in ethnically diverse asthmatics.
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 (FEV(1))/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 PC(20)) 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.


CONCLUSIONS
These data suggest a role for CASP10 as a potential modifier of the asthma phenotype, specifically with measures of airway obstruction and BHR.
Smith
Alicia K
AK
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
Lange
Leslie A
LA
Ampleford
Elizabeth J
EJ
Meyers
Deborah A
DA
Bleecker
Eugene R
ER
Howard
Timothy D
TD
D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics; D001249:Asthma / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000235:genetics* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics; D053455:Caspase 10 / Q000235:genetics*; D053181:Caspase 8 / Q000235:genetics*; D002648:Child; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D005787:Gene Frequency; D006239:Haplotypes; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics / Q000276:immunology*; D014797:Vital Capacity / Q000502:physiology; D044465:White People / Q000235:genetics; D055815:Young Adult
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; C505530:CASP8 protein, human; D053455:Caspase 10; D053181:Caspase 8; C506438:CASP10 protein, human