Abstract
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.
Highlights
Left ventricular (LV) diastolic dysfunction is an increasingly prevalent disease process in hypertensive patients[1]
In this study we assessed the clinical significance of the single nucleotide polymorphisms reflecting different pathophysiological pathways in diastolic heart failure (HF) as complications of hypertension: 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) TGFβ rs1800471], endothelial function [-786 T/C nitric oxide synthase (NOS) rs2070744), glucose and lipid metabolism [Pro12Ala peroxisome proliferator-activated receptor gamma (PPARγ) rs1801282), and vitamin D metabolism [cytochrome P450 27B1 (CYP27B1) C-1260A]
5.5% in C-1260A of CYP27B1 were AA homozygotes and 1% in NOS3–786 C/T rs2070744 were CC homozygotes; in these single nucleotide polymorphisms (SNPs) there was the highest number of heterozygotes (Table 3)
Summary
Left ventricular (LV) diastolic dysfunction is an increasingly prevalent disease process in hypertensive patients[1]. In HFpEF, extracardiac comorbidities such as metabolic risk, arterial hypertension, and renal insufficiency drive left ventricular remodeling and dysfunction through systemic inflammation and coronary microvascular endothelial dysfunction. The latter affects left ventricular diastolic dysfunction through macrophage infiltration, resulting in interstitial fibrosis, and through altered paracrine signaling to cardiomyocytes, which become hypertrophied and stiff because of low nitric oxide and cyclic guanosine monophosphate. In this study we assessed the clinical significance of the single nucleotide polymorphisms reflecting different pathophysiological pathways in diastolic HF as complications of hypertension: 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) TGFβ rs1800471], endothelial function [-786 T/C nitric oxide synthase (NOS) rs2070744), glucose and lipid metabolism [Pro12Ala peroxisome proliferator-activated receptor gamma (PPARγ) rs1801282), and vitamin D metabolism [cytochrome P450 27B1 (CYP27B1) C-1260A]. Our polymorphisms selection we was based on careful analysis of literature in the context of diastolic HF potential patomechanisms and pathogenetic mechanisms[2,3,4]
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