Evidence for CTLA4 as a susceptibility gene for dilated cardiomyopathy.

The cytotoxic T-lymphocyte antigen 4 (CTLA4) is an inhibitory receptor expressed on activated T cells with downregulatory properties. The aim of this study was to analyse whether single-nucleotide polymorphisms (SNPs) within the CTLA4 gene are associated with the diagnosis and disease course of dilated cardiomyopathy (DCM). In two independent cohorts of DCM patients (n=251 and 223) and healthy controls (n=591), the promoter and all four exons of the CTLA4 gene, including their flanking regions, were genotyped, and the resulting allele and genotype distributions of the identified SNPs were compared between the groups. We confirmed two known SNPs in the promoter region (-318C>T) and in exon 1 (+49A>G;Thr17Ala). The allelic frequencies and genotypic distribution of the promoter SNP were similar for DCM patients compared with controls. However, the G/G genotype of the Thr17Ala variant was significantly more frequent in DCM patients compared with controls (37 out of 251 patients (14.7%) versus 44 out of 591 controls (7.4%), P=0.005). The higher frequency of the G/G genotype was confirmed in an additional DCM cohort (29 out of 223 patients (13.0%), P=0.039), indicating that this SNP functions as a risk factor for DCM. At follow-up after 1 year, the ejection fraction and the end-diastolic diameter of the left ventricle did not differ significantly between DCM patients carrying the G/G genotype versus other genotypes (n=199). Our data indicate that the common CTLA4 variant, Thr17Ala, confers susceptibility for DCM, but does not seem to influence the course of the disease 1 year after diagnosis.