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 hyperresponsiveness ( 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.