Human leukocyte antigen (HLA) has been reported to be associated with the pathogenesis of autoimmune-associated idiopathic dilated cardiomyopathy (IDC). However, the HLA-G in this context is limited. In the current study, a total of 117 IDC patients and age and sex matched 401 unrelated healthy controls in a Chinese Han population were HLA-G genotyped for the 14 bp insertion and deletion polymorphism. IDC patients showed markedly increased frequencies of -14 bp/-14 bp genotype [Pc = 0.00049, odds ratio (OR) = 2.17] and -14 bp alleles (Pc = 4.1 x 10(-5), OR = 1.97) when compared with healthy controls. Whereas the frequencies of +14 bp/+14 bp genotype (Pc = 0.0036, OR = 0.35) and +14 bp alleles (Pc = 4.1 x 10(-5), OR = 0.51) were significantly lower in IDC. These data, for the first time, indicated that 14 bp insertion/deletion polymorphism in HLA-G gene could be a genetic risk factor for the susceptibility to IDC.