FC(EPSILON)R1-BETA POLYMORPHISM AND TOTAL SERUM IGE LEVELS IN ENDEMICALLY PARASITIZED AUSTRALIAN ABORIGINES

Endemic helminthic infection is a major public-health problem and affe cts a large proportion of the world's population. In Australia, helmin thic infection is endemic in Aboriginal communities living in tropical northern regions of the continent. Such infection is associated with nonspecific (polyclonal) stimulation of IgE synthesis and highly eleva ted total serum IgE levels. There is evidence that worm-infection vari ance (i.e., human capacity of resistance) and total serum IgE levels m ay be related to the presence of a major codominant gene. The beta cha in of the high-affinity IgE receptor, Fc(epsilon)R1-beta, has been pre viously identified as a candidate for the close genetic linkage of the 11q13 region to IgE responses in several populations. We show a biall elic RsaI polymorphism in Fc(epsilon)R1-beta to be associated with tot al serum IgE levels (P =.0001) in a tropical population of endemically parasitized Australian Aborigines (n = 234 subjects). The polymorphis m explained 12.4% of the total residual variation in serum total IgE a nd showed a significant (P =.0000) additive relationship with total se rum IgE levels, across the three genotypes. These associations were in dependent of familial correlations, age, gender, racial admixture, or smoking status. Alleles of a microsatellite repeat in intron 5 of the same gene showed similar associations. The results suggest that variat ion in Fc(epsilon)R1-beta may regulate IgE-mediated immune responses i n this population.