Genetic predisposition in patients with hypertension and normal ejection fraction to oxidative stress

Ádám Fazakas, Zsuzsanna Szelényi, G. Szénási, Gábor Nyíro, Péter M. Szabó, A. Patócs, Narcis Tegze, Bertalan C. Fekete, A. Molvarec, B. Nagy, J. Jakus, Ferenc Örsi, I. Karádi, András Vereckei

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3 Citations (Scopus)

Abstract

The role of oxidative stress (OXS) due to myocardial nitric oxide synthase (NOS) uncoupling related to oxidative depletion of its cofactor tetrahydrobiopterin (BH4) emerged in the pathogenesis of heart failure with preserved ejection fraction. We determined the prevalence of six single nucleotide polymorphisms (SNPs) of genes encoding enzymes related to OXS, BH4 metabolism, and NOS function in ≥60-year-old 94 patients with hypertension and 18 age-matched controls with normal ejection fraction. Using echocardiography, 56/94 (60%) patients with hypertension had left ventricular (LV) diastolic dysfunction (HTDD+ group) and 38/94 (40%) patients had normal LV diastolic function (HTDD- group). Four SNPs (rs841, rs3783641, rs10483639, and rs807267) of guanosine triphosphate cyclohydrolase-1, the rate-limiting enzyme in BH4 synthesis, one (rs4880) of manganese superoxide dismutase, and one (rs1799983) of endothelial NOS genes were genotyped using real-time polymerase chain reaction method and Taqman probes. Protein carbonylation, BH4, and total biopterin levels were measured from plasma samples. No between-groups difference in minor allele frequency of SNPs was found. We calculated a genetic score indicating risk for OXS based on the minor allele frequencies of the SNPs. A high genetic risk for OXS was significantly associated with HTDD+ even after adjustment for confounding variables (odds ratio [95% confidence interval]:4.79 [1.12-20.54]; P =.035). In both patient groups protein carbonylation (P 4 (P

Original languageEnglish
Pages (from-to)124-132
Number of pages9
JournalJournal of the American Society of Hypertension
Volume10
Issue number2
DOIs
Publication statusPublished - Feb 1 2016

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Keywords

  • Heart failure with preserved ejection fraction
  • hypertension
  • oxidative stress

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Internal Medicine

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