The -17 T/C chemokine receptor 3 genetic polymorphism is associated asthma but not atopy: transmission and association studies.
We genotyped and identified the asthma and atopic status and related phenotypes of 154 nuclear families (453 individuals) each containing at least two affected children with physician-diagnosed asthma (PDA) in order to confirm or refute the possible relevance of known single nucleotide polymorphisms (SNPs) in the gene coding for the CCR3 receptor. Allelic quantification for each SNP by DNA pooling identified -17/TC as the only allele with a clinically relevant frequency in this population with a frequencies of 0.142 in cases of PDA and 0.035 in asymptomatic controls. The whole population frequency of the -17/TC polymorphism was 13.9% and the functional binding site analyses by MatInd and MatInspector programs found that it belonged to the same family as activating transcription factor 6 (ATF-6). The pedigree disequilibrium test (PDT) was applied in 34 informative families and the mutant allele was preferentially transmitted with PDA (P = 0.0001) with methacholine bronchial hyperresponsiveness (BHR) (0.002) but not with markers of atopy as assessed by allergen skin prick tests (SPT) or elevated serum IgE. Case-control analyses in 303 unrelated parents (34-61y [median 43y]) revealed a significant association with both atopic and non atopic asthma (P = 0.001), and in 150 unrelated child probands for non-atopic asthma (P = 0.001). The mutant allele was associated with BHR, with baseline Forced Expiratory Volume in the first second (FEV1) below the population median value but not with atopy defined SPT or elevated serum IgE (>100 IU/ml). The T17C chemokine receptor 3 polymorphism appears to be associated with asthma BHR and disease severity but not with atopy.
Al-Abdulhadi
S A
SA
Molecular Genetic Section & Genetic Counseling Clinic, Department of Pathology & Laboratory Medicine, Saad Specialist Hospital, Al-Khubar, Saudi Arabia.
Al-Rabia
M W
MW
D051702:Activating Transcription Factor 6 / Q000235:genetics / Q000276:immunology; D000293:Adolescent; D000483:Alleles; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D054397:Receptors, CCR3 / Q000235:genetics* / Q000276:immunology; D012720:Severity of Illness Index; D055815:Young Adult
C497111:ATF6 protein, human; D051702:Activating Transcription Factor 6; C515350:CCR3 protein, human; D054397:Receptors, CCR3