The study aimed to assess the clinical significance of selected single nucleotide polymorphisms (SNPs) in patients with diastolic heart failure (HF): inflammation [-174 G/C Interleukin -6 (IL-6) rs1800795, tumor necrosis factor (TNF)-608 G/A rs1800629], fibrosis [Arg25Pro transforming growth factor β (TGF β) rs1800471], endothelial function [-786 T/C nitric oxide synthase (NOS) rs2070744], glucose and lipid metabolism [Pro12Ala peroxisome proliferator activated receptor (PPAR)γ rs1801282], and vitamin D metabolism [cytochrome P450 27B1 (CYP27B1) C-1260A].110 patients with HF with preserved and mid-range ejection fraction (HFpEF and HFmrEF) were recruited. GG homozygotes in 174 G/C of IL6 polymorphism are characterized by higher values of estimated glomerular filtration rate based on the study Modification of Diet in Renal Disease (eGFR MDRD) and C allele in the NOS polymorphism and AA profile in C-1260A of CYP27B1 polymorphism correlated with a lower eGFR (MDRD). In multivariate analysis the CG genotype for 174 G/C of IL-6 and allele A in C-1260A of CYP27B1 are the only SNPs independently associated with worse course of HFpEF and HFmrEF. These data confirm the importance of the selected SNPs in aggravation and complications of hypertension.