Polymorphisms of the IL-4, TNF-alpha, and Fc epsilon RI beta genes and therisk of allergic disorders in at-risk infants

Polymorphisms in the TNF-alpha (A-308C), IL-4 (C-589T), and Fc epsilon RI b eta (E237G) genes have been associated with asthma and related phenotypes. To determine the predictive value of these polymorphisms we have assessed t heir 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 d iseases 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 n o differences in the prevalence of any phenotype between genotypes of the T NF-alpha and Fc epsilon RI beta polymorphisms. However, we found that the I L4-589*T allele was associated with "probable" asthma (RR = 4.1) and that h omozygotes for the IL4-589*T allele had an increased risk for the developme nt of rhinitis (RR = 2.4). Using the transmission disequilibrium test, an a ssociation of IL4-589*T with atopy was found. We conclude that IL-4-589*T, but not TNF-alpha-308*2 or Fc epsilon RI beta*G, is a risk factor for the d evelopment of atopy, asthma, and rhinitis by 12 mo of age.