A common exonic variant of interleukin21 confers susceptibility to atopic asthma.

BACKGROUND:Interleukin (IL)-21, an IL-2 family multifunctional cytokine, is produced by activated CD4+ T cells and is known to potentially affect growth, survival and function of numerous immune cells. As IL-21 regulates IgE production, a key mediator of various allergic disorders and asthma, it is a prime candidate gene for studying atopic asthma. METHODS:In atopic asthma, analyses of four single nucleotide polymorphisms (SNP; C1455T, G1472T, C5250T and C8381T), a tetranucleotide microsatellite repeat (GAAT)(n) and their haplotypes were performed, and serum total IgE (TsIgE) was determined in ethnically matched unrelated patients (n = 255), unrelated controls (n = 245) and nuclear families (n = 140). Correlation between an exonic SNP C5250T in the asthmatics with serum IL-21 levels was also made. RESULTS:In both the case-control and family study groups, the exon-3 polymorphism C5250T of the IL21 gene was significantly associated with atopic asthma and TsIgE. The C5250T polymorphism was found to affect the concentration of serum IL-21 levels in atopic asthmatics. Also, this observation was supported by the structural alteration in IL21 mRNA as predicted by mfold software. Further, our haplotypic studies indicated that while minor haplotypes 4_C_T_C_C and two locus haplotype T_C were associated with asthma in the case-control cohort, none of the major haplotypes was found to be associated with either asthma or TsIgE levels. CONCLUSION:Our study provides evidence that IL21 is associated with atopic asthma, TsIgE and serum IL-21 levels. Thus, it may initiate further research to elucidate the role of the IL21 gene in asthma pathogenesis.

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