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

AimsTo identify potential genetic associations of five cytokine gene polymorphisms with disease severity and prognosis in patients with idiopathic dilated cardiomyopathy (DCM).Methods and resultsEighty patients with DCM were genotyped for transforming growth factor beta1 (TGF-β1) +869 T/C (codon10 Leu → Pro), TGF-β1 +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-β1 +869 T/C polymorphism mean VO2 max was significantly higher than in CC homozygous patients (25.67 ± 6.73 ml/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-β1 +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-β1 +869 T/C and TGF-β1 +915 G/C genotypes were associated with adverse outcome (p = 0.014).ConclusionSpecific cytokine gene polymorphisms seem to be associated with worse prognosis as well as with measures of disease severity in DCM.

Research highlights► Specific gene polymorphisms are associated with disease severity and prognosis in dilated cardiomyopathy. ► TGF-β1 polymorphisms are associated with worse exercise capacity, symptoms and outcome. ► IL-6 polymorphism negatively influences left ventricular dimensions. ► IFN-g polymorphism is associated with poor prognosis.