Association between a new polymorphism in the activation-induced cytidine deaminase gene and atopic asthma and the regulation of total serum IgE levels

Background: Activation-induced cytidine deaminase (AICDA) is a recently ide ntified RNA-editing deaminase that plays an important role in class-switchi ng. 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 seru m IgE and development of atopic asthma. Methods: We screened for polymorphisms in the 5 ' -flanking and coding regi ons of the AICDA gene in subjects with atopic asthma and analyzed the effec t of these polymorphisms on the development of atopic asthma and on total s erum 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 disequilibr ium testing showed that the 7888C allele was transmitted preferentially to asthma-affected children (P = .007). Mean log [total serum IgE] levels of p arents with the 7888C/7888C, 7888C/7888T, and 7888T/7888T genotypes were 2. 12, 1.99, and 1.77, respectively, and a significant association was observe d 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 pa irs) and the other lacking the first 30 base pairs of exon 4 (variant 2; 45 3 base pairs). These variants were not associated with the 7888C/T polymorp hism. Conclusion: The 7888C/T polymorphism might be associated with the pathogene sis of atopic asthma and the regulation of total serum IgE levels.