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

Genes & Immunity volume 6, pages 24–30 (2005)Cite this article

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 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.

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Acknowledgements

GlaxoSmithKline Research and development and the Scottish Heart Chest and Stroke Association supported the family collection. We thank Julie Black and Joanna Gordon for valuable assistant in family recruitment.

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  1. Department of Child Health, University of Aberdeen, Royal Aberdeen Children Hospital, Westburn Road, Aberdeen, Scotland, UK

    S A Al-Abdulhadi, P J Helms, M Main, O Smith & G Christie

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  1. S A Al-Abdulhadi
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Correspondence to S A Al-Abdulhadi.

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Al-Abdulhadi, S., Helms, P., Main, M. et al. Preferential transmission and association of the −403 G → A promoter RANTES polymorphism with atopic asthma. Genes Immun 6, 24–30 (2005). https://doi.org/10.1038/sj.gene.6364151

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