Human Genetics

, Volume 107, Issue 6, pp 591–596

Association of the TNF-α-308 (G→A) polymorphism with self-reported history of childhood asthma

  • Elizabeth C. Winchester
  • Iona Y. Millwood
  • Lucinda Rand
  • Michelle A. Penny
  • Anna M. Kessling
Original Investigations
  • 100 Downloads

Abstract

Asthma is a complex disease involving genetic and environmental aetiology. The tumour necrosis factor-alpha (TNF- α) and angiotensin-converting enzyme (ACE) genes have been implicated in asthma pathogenesis. This study investigated the association of a G-308A variant of TNF- α and an insertion/deletion (I/D) variant of ACE with a self-reported history of childhood asthma, in two population groups. At Northwick Park Hospital, London, 1,811 pregnant women attending for antenatal care were recruited. Participants with a self-reported history of childhood asthma, determined by a researcher-administered questionnaire, and controls with no personal or family history of asthma, of UK/Irish (cases n=20; controls n=416) and South Asian (cases n=6; controls n=275) origin were used in this study. Participants were genotyped for the TNF-α-308 and ACE I/D variants by a PCR-RFLP and PCR approach. The TNF-α-308 allele 2 (−308A) was significantly associated with self-reported childhood asthma in the UK/Irish (Odds ratios (OR): 2.6; 95% confidence intervals (CI): 1.1–6.2; P=0.03) but not in the South Asian population. The ACE DD genotype was not associated with childhood asthma in either population group. Gametic phase disequilibrium between the TNF-α-308 and ACE I/D variants was significantly different from zero in UK/Irish cases (Δ=0.09; P=0.034). The TNF-α-308 allele 2 or a linked major histocompatibility complex (MHC) variant may be a genetic risk factor for childhood asthma in the UK/Irish sample.

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Copyright information

© Springer-Verlag 2000

Authors and Affiliations

  • Elizabeth C. Winchester
    • 1
  • Iona Y. Millwood
    • 1
  • Lucinda Rand
    • 1
  • Michelle A. Penny
    • 1
  • Anna M. Kessling
    • 1
  1. 1.Department of Medical and Community GeneticsImperial College School of Medicine, Kennedy Galton CentreHarrowUK

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