Ec. Winchester et al., Association of the TNF-alpha-308 (G -> A) polymorphism with self-reported history of childhood asthma, HUM GENET, 107(6), 2000, pp. 591-596
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.