Polymorphisms in the SOD2 and HLA-DRB1 genes are associated with nonfamilial idiopathic dilated cardiomyopathy in Japanese

To reveal genetic risk factors of nonfamilial idiopathic cardiomyopathy (ID C) in Japanese, polymorphisms in the SOD2 and HLA-DRB1 genes were investiga ted in 86 patients and 380 healthy controls. There was a significant excess of homozygotes for the V allele [Val versus Ala (A allele), a polymorphism in the leader peptide of manganese superoxide dismutase at position 16] of the SOD2 gene in the patients compared with the controls (87.2% versus 74. 7%, odds ratio = 2.30, p = 0.013, pc < 0.03), and a significant increase in the frequency of HLA-DRB1*1401 in the patients was confirmed (14.0% vs 4.5 %, odds ratio = 3.46, p = 0.001, pc < 0.03). A two-locus analysis suggested that these two genetic markers (SOD2-VV genotype and DRB1*1401) may play a synergistic role in controlling the susceptibility to nonfamilial IDC. In addition, processing efficiency of Val-type SOD2 leader peptide in the pres ence of mitochondria was significantly lower than that of the Ala-type by 1 1 +/- 4%, suggesting that this lower processing efficiency was in part an u nderlying mechanism of the association between the SOD2-VV genotype and non familial IDC. (C) 1999 Academic Press.