M. Ito et al., Polymorphisms of tumor necrosis factor-alpha and interleukin-10 genes in Japanese patients with idiopathic dilated cardiomyopathy, JPN HEART J, 41(2), 2000, pp. 183-191
Various cytokines play important roles in the pathogenesis of congestive he
art failure, TNF-alpha is one of the pro-inflammatory cytokines, and IL-10
has anti-inflammatory actions. The -308 (G / A) polymorphism of the TNF-or
gene (TNFA 1 and A2) and the single base -1082 (G i 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-alpha and IL-10, respectively. We examined
TNF-alpha and IL-10 gene polymorphisms using a polymerase chain reaction-r
estriction fragment length polymorphism technique in 48 Japanese patients w
ith idiopathic dilated cardiomyopathy. The frequency of these polymorphisms
was compared with 50 healthy Japanese. The clinical courses, such as disea
se onset, left ventricular function, progression during the follow up perio
d and hospitalization from congestive heart failure, were also analyzed. Se
rum TNF-alpha levels were measured using an enzyme-linked immunosorbent ass
ay (ELISA) technique in the patients with idiopathic dilated cardiomyopathy
to reveal the correlation with genotypes. Patients with ischemic cardiomyo
pathy or other secondary cardiomyopathies were excluded from this study. Th
e allele frequency of TNFA2 in idiopathic dilated cardiomyopathy was signif
icantly higher than that of the healthy group (13.5 % and 3.0 %, respective
ly, 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 asso
ciated with the clinical course. Serum TNF-alpha levels were elevated in th
e patient group compared with the healthy group. There were no differences
in serum TNF-alpha levels between the patients with TNFA1 and those with TN
FA2. In conclusion, the TNFA2 allele may be linked to the pathogenesis of i
diopathic dilated cardiomyopathy in Japanese patients.