RESUMEN
BACKGROUND: Activation-induced cytidine deaminase (AICDA) is a recently identified RNA-editing deaminase that plays an important role in class-switching. Defects in AICDA result in a hyper-IgM phenotype and lack of IgG, IgA, and IgE in both human beings and mice. OBJECTIVE: The aim of this study was to determine whether the AICDA gene is related to regulation of total serum IgE and development of atopic asthma. METHODS: We screened for polymorphisms in the 5;-flanking and coding regions of the AICDA gene in subjects with atopic asthma and analyzed the effect of these polymorphisms on the development of atopic asthma and on total serum IgE levels in Japanese asthmatic families. RESULTS: We identified 3 novel polymorphisms (5923A/G, 7888C/T, and 8578A/C) and 1 rare variant (Arg25Cys) in the AICDA gene. Transmission disequilibrium testing showed that the 7888C allele was transmitted preferentially to asthma-affected children (P =.007). Mean log [total serum IgE] levels of parents with the 7888C/7888C, 7888C/7888T, and 7888T/7888T genotypes were 2.12, 1.99, and 1.77, respectively, and a significant association was observed between the genotypes (P =.02). In RT-PCR experiments, we found 2 novel splice variants of AICDA, one lacking all of exon 4 (variant 1; 367 base pairs) and the other lacking the first 30 base pairs of exon 4 (variant 2; 453 base pairs). These variants were not associated with the 7888C/T polymorphism. CONCLUSION: The 7888C/T polymorphism might be associated with the pathogenesis of atopic asthma and the regulation of total serum IgE levels.