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

Asthma is a complex disease involving genetic and environmental aetiology. The tumour necrosis factor-alpha (TNF-alpha) and angiotensin-converting enz yme (ACE) genes have been implicated in asthma pathogenesis. This study inv estigated 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 as thma, in two population groups. At Northwick Park Hospital, London, 1,811 p regnant women attending for antenatal care were recruited. Participants wit h a self-reported history of childhood asthma, determined by a researcher-a dministered 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 geno typed for the TNF-alpha -308 and ACE I/D variants by a PCR-RFLP and PCR app roach. The TNF-alpha -308 allele 2 (-308A) was significantly associated wit h 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 po pulation. The ACE DD genotype was not associated with childhood asthma in e ither 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-alpha -308 allele 2 or a linked majo r histocompatibility complex (MHC) variant may be a genetic risk factor for childhood asthma in the UK/Irish sample.