3'-UTR OLR1/LOX-1 gene polymorphism and endothelial dysfunction: molecular and vascular data in never-treated hypertensive patients.
Endothelial dysfunction represents an independent predictor for clinical events. Genetic background may promote deleterious alterations of endothelial physiology. The aim of the study was to investigate the relationship between the rs1050283 polymorphism in the 3'-UTR of OLR1/LOX-1 gene and endothelial dysfunction in 178 never-treated hypertensive patients and 36 healthy subjects. The rs1050283 C/T single nucleotide polymorphism was detected, by TaqMan allelic discrimination assay. The influence of polymorphism on gene transcription rate was tested in 12 heterozygous hypertensive patients, by using an allelic imbalance assay. Forearm blood flow (FBF) was measured during intra-arterial infusion of acetylcholine (ACh), and sodium nitroprusside at increasing doses. Analysis of endothelium-dependent and endothelium-independent vasodilatation was tested according to rs1050283 polymorphism. In hypertensive patients, ACh-stimulated FBF is significantly reduced in T allele carriers (P < 0.0001), even when the allelic imbalance assay indicates an overexpression of C allele. In healthy subjects, there is no significant difference for ACh-dependent vasodilatation among genotypic groups (P = 0.660). In essential hypertensive patients, the T allele of OLR1/LOX-1 gene is strongly associated with an impaired endothelium-dependent vasodilatation, a powerful predictor of cardiovascular events.
Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, V.le Europa, 88100, Catanzaro, Italy.
Angela
A
Sciacqua
Ivan
I
Presta
Maria
M
Perticone
Eliezer J
EJ
Tassone
Francesco
F
Andreozzi
Maria Chiara
MC
Quitadamo
Federica Carla
FC
Sangiuolo
Giorgio
G
Sesti
Francesco
F
Perticone
D020413:3' Untranslated Regions / Q000235:genetics*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051127:Scavenger Receptors, Class E / Q000235:genetics*; D014664:Vasodilation
D020413:3' Untranslated Regions; C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E