Association Of The Single Nucleotide Polymorphisms Of Interleukin-2 Gene Promoter Region With Idiopathic Dilated Cardiomyopathy

Background and Objective Idiopathic dilated cardiomyopathy (IDCM)is one of the leading causes of severe heart failure and the most commoncause of heart transplantation due to its ventricular dilatation and contractiledysfunction. Although its pathogenesis remains uncertain, three factors havecurrently been identified to be potentially important: genetic factors, viralinfection, and autoimmune mechanism. It has been shown that overactivationof T lymphocytes plays a major role in the pathogenesis. Interleukin-2 (IL-2)is a critical cytokine for T cell activation. Abnormally high level of IL-2 wasobserved in IDCM patients. Single nucleotide polymorphisms (SNPs) in IL-2gene promoter region influence the production of IL-2 and are associated with certain autoimmune diseases mediated by T lymphocyte. So far, both athome and abroad there is no report of the relationship between the SNPs ofIL-2 gene promoter region and IDCM. By investigating the association ofIL-2-384T/G, -475A/T and -631G/A polymorphisms in the promoter regionwith IDCM in southwestern Chinese Han population, this study intends toexplore the immunogenetic pathogenesis of IDCM.Methods We genotype three SNPs of IL-2 gene at position -384, -475and -631 with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 109 IDCM patients and 210 unrelated healthysubjects in Han population of southwestern China, and choose the representative PCR products with variant patterns for direct sequencing. The genotypefrequencies and the allele frequencies are statistically compared betweenIDCM patients and control groups by X~2 test.Resultsâ‘ Compared with controls, the frequency of TT and TGgenotypes (0.9541 in patients vs. 0.8762 in controls, P=0.042) and thefrequency ofT allele (0.7294 in patients vs. 0.6452 in controls, P=0.039) atposition -384 in IL-2 gene promoter region are significantly increased inIDCM patients.â‘¡All the studied samples at -631 locus have GG genotype,and for the -475 locus, only two heterozygous individuals (AT) in the control group are found, the rest of the samples carrying the AA genotype; Nodifferences of the SNP genotype or allele frequencies at these two loci aredetected between IDCM and control groups.Conclusion These data indicate, for the first time, the relevance of theIL-2 gene SNPs with human IDCM. IL-2 gene -384T/G polymorphism in thepromoter region is associated with the pathogenesis of IDCM in southwesternChinese Han population. The presence of Y allele may represent a risk factorfor IDCM.