Am. J. Respir. Crit. Care Med., Volume 161, Number 5, May 2000, 1655-1659

Polymorphisms of the IL-4, TNF-, and Fc RI Genes and the Risk of Allergic Disorders in At-risk Infants

SHOUKANG ZHU, MOIRA CHAN-YEUNG, ALLAN B. BECKER, HELEN DIMICH-WARD, ALEXANDER C. FERGUSON, JURE MANFREDA, WADE T. A. WATSON, PETER D. PARÉ, and ANDREW J. SANDFORD

Pulmonary Research Laboratory, St. Paul's Hospital, and Occupational and Environmental Lung Diseases Unit, Department of Medicine, University of British Columbia, Vancouver, British Columbia; Section of Allergy and Clinical Immunology, Department of Pediatrics, University of Manitoba, Winnipeg, Manitoba, Canada

Polymorphisms in the TNF- (A-308G), IL-4 (C-589T), and Fc RI (E237G) genes have been associated with asthma and related phenotypes. To determine the predictive value of these polymorphisms we have assessed their relative risk (RR) for the development of atopy, asthma, and rhinitis in a high-risk infant population that is being followed longitudinally from birth. DNA was extracted and genotyped for 373 infants and 572 parents for each polymorphism. Phenotypic data were collected for atopy and allergic diseases in the infants at 12 mo of age. The prevalence of these phenotypes in the 281 white infants was compared in each genotypic group. There were no differences in the prevalence of any phenotype between genotypes of the TNF- and Fc RI polymorphisms. However, we found that the IL4-589*T allele was associated with "probable" asthma (RR = 4.1) and that homozygotes for the IL4-589*T allele had an increased risk for the development of rhinitis (RR = 2.4). Using the transmission disequilibrium test, an association of IL4-589*T with atopy was found. We conclude that IL-4-589*T, but not TNF--308*2 or Fc RI*G, is a risk factor for the development of atopy, asthma, and rhinitis by 12 mo of age.

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