title: Association of the TNF-alpha-308 (G-->A) polymorphism with self-reported history of childhood asthma.
abstract: Asthma is a complex disease involving genetic and environmental aetiology. The tumour necrosis factor-alpha (TNF-alpha) and angiotensin-converting enzyme (ACE) genes have been implicated in asthma pathogenesis. This study investigated the association of a G-308A variant of TNF-alpha 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-alpha-308 and ACE I/D variants by a PCR-RFLP and PCR approach. The TNF-alpha-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-alpha-308 and ACE I/D variants was significantly different from zero in UK/Irish cases (delta=0.09; P=0.034). The TNF-alpha308 allele 2 or a linked major histocompatibility complex (MHC) variant may be a genetic risk factor for childhood asthma in the UK/Irish sample.
authors.affiliation: Department of Medical and Community Genetics, Imperial College School of Medicine, Kennedy Galton Centre, Northwest London Hospitals NHS Trust, Harrow, UK.
authors.forename: E C
authors.initials: EC
authors.lastname: Winchester
authors.forename: I Y
authors.initials: IY
authors.lastname: Millwood
authors.forename: L
authors.initials: L
authors.lastname: Rand
authors.forename: M A
authors.initials: MA
authors.lastname: Penny
authors.forename: A M
authors.initials: AM
authors.lastname: Kessling
mesh_terms: D000225:Adenine; D001208:Asia; D001249:Asthma / Q000235:genetics*; D002648:Child; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005838:Genotype; D006147:Guanine; D006801:Humans; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011247:Pregnancy; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D006113:United Kingdom
chemical_list: D014409:Tumor Necrosis Factor-alpha; D006147:Guanine; D007703:Peptidyl-Dipeptidase A; D000225:Adenine