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Thorax 2009;64:381-387 doi:10.1136/thx.2008.102053
  • Asthma

Positionally cloned asthma susceptibility gene polymorphisms and disease risk in the British 1958 Birth Cohort

  1. J D Blakey1,
  2. I Sayers1,
  3. S M Ring2,
  4. D P Strachan3,
  5. I P Hall1
  1. 1
    Division of Therapeutics and Molecular Medicine, Nottingham Respiratory Biomedical Research Unit, University Hospital Nottingham, Nottingham, UK
  2. 2
    Department of Community Based Medicine, University of Bristol, UK
  3. 3
    Division of Community Health Sciences, St George’s Hospital, University of London, UK
  1. Professor I P Hall, Division of Therapeutics and Molecular Medicine, Nottingham Respiratory Biomedical Research Unit, University Hospital Nottingham, Nottingham NG7 2UH, UK; Ian.Hall{at}nottingham.ac.uk
  • Received 20 May 2008
  • Accepted 24 January 2009
  • Published Online First 22 February 2009

Abstract

Objective: The aim of this study was to estimate the contribution of polymorphisms in the positionally cloned asthma candidate genes ADAM33, PHF11, DPP10, GPRA and PTGDR to the risk of asthma, total and specific immunoglobulin E level, lung function and wheezing in a large, nationally representative, population.

Methods: An association analysis was undertaken using genotype data for tagging and previously associated single nucleotide polymorphisms (SNPs) in regions of these genes and longitudinal phenotype data from singletons of white ethnicity in the British 1958 Birth Cohort DNA archive (n = 7703). Population-attributable risk fractions for SNPs showing association were calculated.

Results: Polymorphisms producing small but statistically significant increases in asthma risk (OR 1.1 per allele) were identified in DPP10 and ADAM33, with the strongest evidence being for SNPs tagging the DPP10 gene. No individual SNP in any gene under study markedly increased risk for any of the phenotypes in the population studied.

Conclusions: These data suggest that DPP10 and ADAM33 influence asthma risk in the UK population. However, the effects driven by any given locus are small, and genotyping of multiple polymorphisms in many genes will be needed to define a full genetic profile for disease risk.

Footnotes

  • Additional figures are published online only at http://thorax.bmj.com/content/vol64/issue5

  • Competing interests: None.

  • Ethics approval: Protocols for the 2002–2004 biomedical examination were approved by the South East MultiCentre Research Ethics Committee. The present study was approved by the oversight committee for the biomedical examination of the British 1958 Birth Cohort.

  • Patient consent: All participants gave informed written consent to participate in genetic association studies.

  • Contributors: JB, IPH and DPS designed this study. DPS and SMR were responsible for the management of the 1958 birth cohort genetic resource. SNP selection was performed by JB and IS. JB was responsible for genetic data handling. Statistical analysis was performed by DPS with input from IPH. The manuscript was drafted by IPH and JB: all authors reviewed and revised the manuscript and approved the final version.

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  6. All Versions of this Article:
    1. thx.2008.102053v1
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