Preferential transmission and association of the -403 G-A promoter RANTES polymorphism with atopic asthma

Saleh Al-Abdulhadi, Peter Joseph Benedict Helms, Margaret Jessie Campbell Main, O. O. Smith, G. Christie

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Abstract

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.

Original languageEnglish
Pages (from-to)24-30
Number of pages6
JournalGenes and Immunity
Volume6
DOIs
Publication statusPublished - 2005

Keywords

  • RANTES promoter
  • polymorphism
  • PDT
  • atopy
  • asthma
  • association
  • PEDIGREE DISEQUILIBRIUM TEST
  • CHEMOKINE RANTES
  • CYTOKINE RANTES
  • GENE
  • MIP-1-ALPHA
  • LINKAGE

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