Objective: Endothelial dysfunction and arterial stiffness are early vascular alterations, linked to oxidative stress and inflammation, with prognostic significance in essential hypertensive patients. P2X7 receptors (P2X7R), responding to extracellular ATP, are encoded by a highly polymorphic gene and modulate inflammatory responses and cell growth, potentially playing a role in the control of vascular tone. This study evaluated the effects of P2X7R gene polymorphisms (single nucleotide polymorphisms, SNPs) on a detailed vascular hypertensive phenotype.
Methods: We determined by real-time PCR two SNPs of the P2X7R gene (489C>T and 1513A>C) in 134 newly diagnosed, treatment-naive essential hypertensive patients and 131 normotensive controls (CTL). Endothelium-dependent response was assessed as flow-mediated dilatation (FMD) of the brachial artery, arterial stiffness as aortic pulse wave velocity (PWV) and augmentation index (AIx) by tonometry. Markers of oxidative stress were also measured.
Results: FMD was lower (P < 0.05), whereas aortic PWV and AIx were higher (P < 0.01) in essential hypertensive patients than in CTL. The allelic distribution of the two P2X7R SNPs was similar in essential hypertensive patients and CTL, either concerning homozygosis or presence of the mutant alleles. No difference was observed for FMD, aortic PWV, AIx or markers of oxidative stress between carriers and noncarriers of the mutant alleles, either in essential hypertensive patients and in CTL. In the whole group, logistic regression showed that the mutant allele of 1513A>C was a main determinant of AIx (odds ratio 1.90; P = 0.03).
Conclusion: P2X7R 489C>T and 1513A>C SNPs are not associated with altered endothelial function or arterial stiffness in untreated newly diagnosed essential hypertensive patients; a possible role in influencing peripheral wave reflection should be further addressed.
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
Correspondence to Anna Solini, MD, PhD, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, I-56126 Pisa, Italy. Tel: +39 050993482; fax: +39 050553235; e-mail: firstname.lastname@example.org
Abbreviations: AIx, augmentation index; CTL, normotensive controls; FMD, flow-mediated dilatation; eGFR, estimated glomerular filtration rate; FRAP, ferric reducing antioxidant power; GTN, glyceril trinitrate; LOOH, lipid hydroperoxide; MDA, malondialdehyde; MDRD formula, Modification of diet in renal disease formula; PWV, pulse wave velocity; P2X7R, P2X7 receptors; SNP, single nucleotide polymorphism; TBA, thiobarbituric acid; UACR, urinary albumin to creatinine ratio
Received 13 March, 2013
Revised 1 July, 2013
Accepted 19 July, 2013