Cytokine gene polymorphisms are associated with markers of disease severity and prognosis in patients with idiopathic dilated cardiomyopathy.

ABSTRACT

AIMS: To identify potential genetic associations of five cytokine gene polymorphisms with disease severity and prognosis in patients with idiopathic dilated cardiomyopathy (DCM). METHODS AND RESULTS: Eighty patients with DCM were genotyped for transforming growth factor beta1 (TGF-ß1)+869 T/C (codon10 Leu→Pro), TGF-ß1 +915 G/C (codon25 Arg→Pro), interleukin (IL)-6 -174G/C, tumor necrosis factor-alpha (TNF-α) -308A/G, interferon-gamma (IFN-γ) +874T/A, IL-10 -1082A/G, IL-10 -819T/C and IL-10 -592A/C gene polymorphisms. In homozygous TT patients for TGF-ß1 +869 T/C polymorphism mean VO(2) max was significantly higher than in CC homozygous patients (25.67±6.73ml/kg/min vs. 20.29±6.35 ml/kg/min, p = 0.046), which remained significant only for patients younger than 39 years old after adjusting for age and sex (p = 0.009). C carriers of TGF-ß1 +915 G/C polymorphism are 4.2 times more likely to be in a worse NYHA stage (III-IV) than non C carriers [OR 4.25, 95% CI (1.53-11.80), p = 0.006]. Patients GG homozygous for IL-6 -174G/C polymorphism presented greater left ventricle end-systolic (p = 0.018) and end-diastolic (p = 0.04) diameters in comparison to the CC homozygous. The AA homozygote for IFN-γ +874T/A polymorphism (p = 0.02) and the combination of the TGF-ß1 +869 T/C and TGF-ß1 +915 G/C genotypes were associated with adverse outcome (p = 0.014). CONCLUSION: Specific cytokine gene polymorphisms seem to be associated with worse prognosis as well as with measures of disease severity in DCM.