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.