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

ABSTRACT: 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.To assess the role of genetic variation in CFLAR, CASP10 and CASP8 in asthma and related phenotypes in individuals of diverse ethnic backgrounds.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).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.These data suggest a role for CASP10 as a potential modifier of the asthma phenotype, specifically with measures of airway obstruction and BHR.

SUBMITTER: Smith AK

PROVIDER: S-EPMC3979622 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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

Smith Alicia K AK Lange Leslie A LA Ampleford Elizabeth J EJ Meyers Deborah A DA Bleecker Eugene R ER Howard Timothy D TD

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 20080924 11

<h4>Background</h4>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.<h4>Objective</h4>To assess the role of gene ...[more]

PMID: 18823309

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Project description:BACKGROUND:Respiratory syncytial virus and other respiratory tract viruses lead to common colds in most infants, whereas a minority develop acute severe bronchiolitis often requiring hospitalization. We hypothesized that such an excessive response to respiratory tract viral infection is caused by host factors reflected in pre-existing increased bronchial responsiveness. OBJECTIVE:We sought to compare bronchial responsiveness and lung function in 1-month-old neonates who later develop acute severe bronchiolitis with those who do not. METHODS:We measured infant lung function (n=402) and bronchial responsiveness to methacholine (n=363) using the raised-volume rapid thoracoabdominal compression technique before any respiratory symptoms in 1-month-old neonates from the Copenhagen Prospective Study of Asthma in Childhood birth cohort born to mothers with asthma. The children were prospectively monitored for respiratory symptoms and given a diagnosis of acute severe bronchiolitis according to a fixed algorithm. RESULTS:Thirty-four (8.5%) infants had acute severe bronchiolitis before 2 years of age, 21 (62%) were hospitalized, and 23 (67%) of the cases were associated with respiratory syncytial virus. Children who later had acute severe bronchiolitis irrespective of viral species had a 2.5-fold increased responsiveness to methacholine (provocative dose of methacholine producing a 15% decrease in transcutaneous oxygen pressure [PD(15)]) at age 1 month compared with control subjects (median PD(15) in cases vs control subjects, 0.13 vs 0.33 ?mol; P=.01), whereas differences in baseline airflow were not significant for forced expiratory volume at 0.5 seconds (mean z score for cases vs control subjects, -0.18 vs -0.01; P=.36) and forced expiratory flow at 50% of forced vital capacity (mean z score for cases vs control subjects, -0.37 vs -0.09; P=.13). CONCLUSION:Bronchial hyperresponsiveness in at-risk neonates precedes acute severe bronchiolitis in response to infections with respiratory tract virus.

Dataset Information

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

Publications

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

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