Carotid artery atherosclerosis in hypertensive patients with a functional LDL receptor-related protein 6 gene variant
Received 9 February 2009; received in revised form 17 June 2009; accepted 4 August 2009. published online 15 October 2009. Corrected Proof
Abstract
Background and aims
Rare (611C) and common (1062V) variants of the Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) display reduced activation of Wnt/ß-catenin signaling. The rare gene variant was associated with hypertension, metabolic abnormalities, and early coronary artery disease. We investigated whether the common 1062V LRP6 variant was related to carotid artery atherosclerosis (CAA) in hypertensive patients.
Methods and results
Retrospective study of 334 hypertensive patients (<65 years old) who underwent carotid artery ultrasonography. Hypertension, type 2 diabetes, dyslipidemia, glomerular filtration rate, and smoking habit were evaluated. CAA was defined by the presence of atherosclerotic plaques (focal intima–media thickness ≥1.3mm). Logistic regression models were used to estimate the independent effect of 1062V allele. The relationship between LRP6 genotypes and LRP6 gene expression in carotid plaques was also investigated. No difference was observed between genotypes in clinical variables except for a slightly higher fasting glucose in 1062V carriers. The 1062V LRP6 variant was an independent risk factor for CAA in both unadjusted (OR 2.08, 95%CI 1.27–3.41, p=0.003) and adjusted models (OR 1.92, 95%CI 1.09–3.39, p=0.02). LRP6 was expressed in carotid atherosclerotic plaques at significantly lower levels (p=0.015) in 1062V carriers.
Conclusion
Beside the role of established risk factors, 1062V variant of LRP6 and CAA are strongly associated in hypertensive patients, making LRP6 a novel relevant candidate gene for atherosclerosis in the presence of hypertension.
aDepartment of Internal Medicine, “Hypertension Excellence Centre” of the European Society of Hypertension, University “Politecnica delle Marche”, Ancona, Italy
bDepartment of Vascular Surgery, University “Politecnica delle Marche”, Ancona, Italy
Correspondence to: Department of Internal Medicine, University of Ancona “Politecnica delle Marche”, University Hospital “Ospedali Riuniti”, 60131 Ancona, Italy. Tel.: +39 71 889499; fax: +39 71 889232.
ABSTRACT
mm). Logistic regression models were used to estimate the independent effect of 1062V allele. The relationship between LRP6 genotypes and LRP6 gene expression in carotid plaques was also investigated. No difference was observed between genotypes in clinical variables except for a slightly higher fasting glucose in 1062V carriers. The 1062V LRP6 variant was an independent risk factor for CAA in both unadjusted (OR 2.08, 95%CI 1.27–3.41, p