P2X7 receptor polymorphisms do not influence endothelial function and vascular tone in neo-diagnosed, treatment-naive essential hypertensive patients.
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).


CONCLUSIONS
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.
Lorenzo
L
Ghiadoni
Chiara
C
Rossi
Emiliano
E
Duranti
Eleonora
E
Santini
Rosa Maria
RM
Bruno
Antonio
A
Salvati
Stefano
S
Taddei
Anna
A
Solini
D000328:Adult; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009129:Muscle Tonus; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D058486:Receptors, Purinergic P2X7 / Q000235:genetics*
D058486:Receptors, Purinergic P2X7