Polymorphisms of Tumor Necrosis Factor-α and Interleukin-10 Genes in Japanese Patients with Idiopathic Dilated Cardiomyopathy

Abstract

Various cytokines play important roles in the pathogenesis of congestive heart failure. TNF-α is one of the pro-inflammatory cytokines, and IL-10 has anti-inflammatory actions. The -308 (G/A) polymorphism of the TNF-α gene (TNFA1 and A2) and the single base -1082 (G/A) polymorphism of the IL-10 gene (IL-10 1^*G and 1^*A) have been identified as causing alterations to the in vivo production of TNF-α and IL-10, respectively. We examined TNF-α and IL-10 gene polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism technique in 48 Japanese patients with idiopathic dilated cardiomyopathy. The frequency of these polymorphisms was compared with 50 healthy Japanese. The clinical courses, such as disease onset, left ventricular function, progression during the follow up period and hospitalization from congestive heart failure, were also analyzed. Serum TNF-α levels were measured using an enzyme-linked immunosorbent assay (ELISA) technique in the patients with idiopathic dilated cardiomyopathy to reveal the correlation with genotypes. Patients with ischemic cardiomyopathy or other secondary cardiomyopathies were excluded from this study. The allele frequency of TNFA2 in idiopathic dilated cardiomyopathy was significantly higher than that of the healthy group (13.5% and 3.0%, respectively, p=0.0084). There was no difference in the allele frequency of the IL-10 gene between the two groups. Polymorphism of the TNFA2 gene was not associated with the clinical course. Serum TNF-α levels were elevated in the patient group compared with the healthy group. There were no differences in serum TNF-α levels between the patients with TNFA1 and those with TNFA2. In conclusion, the TNFA2 allele may be linked to the pathogenesis of idiopathic dilated cardiomyopathy in Japanese patients. (Jpn Heart J 2000; 41: 183-191)