Preferential transmission and association of the -403 G --> A promoter RANTES polymorphism with atopic asthma.
Asthma is a complex inherited disease. The study was undertaken to identify the association of RANTES promoter polymorphisms with atopy and asthma using family-based association tests (FBATs) and generation-specific case-control analyses. We identified 154 nuclear families (453 individuals) in whom we established RANTES promoter status using the RFLP-PCR method. Of the two known promoter polymorphisms -403G/A and -28C/G, only the former appeared with a clinically relevant frequency. A total of 61 families were eligible for assessment of transmission of the allele with asthma and atopy by the pedigree disequilibrium test (PDT). Overall, allele frequency for -403A was 38.3% and 84 of 89 (94.3%) alleles were transmitted with physician diagnosed asthma (PDA) (P=0.001). All 89 children with atopy received the mutant allele, which was more than expected following Mendelian Laws of transmission (P=0.0001). In 303 unrelated parents, significant associations of the mutant allele were for atopy with or without asthma (P=0.001). In 150 unrelated children, significant associations were for atopy alone (P=0.001) and asthma (P=0.001). No associations were found for bronchial hyper-responsiveness (BHR). The -403 G --> A is transmitted with atopy and atopic asthma, although its contribution appears to relate more to atopy than asthma and BHR.
Al-Abdulhadi
S A
SA
Department of Child Health, University of Aberdeen, Royal Aberdeen Children Hospital, Aberdeen AB25 2ZG, Scotland, UK. saa@iahs.abdn.ac.uk
Helms
P J
PJ
Main
M
M
Smith
O
O
Christie
G
G
D000293:Adolescent; D000328:Adult; D000483:Alleles; D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D018946:Chemokine CCL5 / Q000235:genetics*; D002648:Child; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
D018946:Chemokine CCL5