1.8 A Functional LDL Receptor-Related Protein 6 Gene Variant is an Independent Risk Factor For Early Carotid Artery Athe
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High Blood Press Cardiovasc Prev 2008; 15 (3): 171-215 1120-9879/08/0003-0171/$48.00/0 © 2008 Adis Data Information BV. All rights reserved.
Atherosclerosis and Inflammation 1.8 A Functional LDL Receptor-Related Protein 6 Gene Variant is an Independent Risk Factor For Early Carotid Artery Atherosclerosis in Hypertensive Patients R. Sarzani (1), F. Salvi (1), M. Bordicchia (1), F. Guerra (1), I. Battistoni (1), L. Roberti (1), M. Fortunati (1), P. Dess`i-Fulgheri (1), A. Rappelli (1) ` Politecnica delle Marche, (1)Clinica di Medicina Interna, Universita Ancona, Italy Introduction. Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) is a co-receptor in the canonical Wnt/beta-catenin signalling pathway. Common (I1062V) and rare (R61 1C) variants display reduced activation Wnt/beta-catenin signalling. The rare gene variant causes hypertension, metabolic abnormalities, and early coronary artery disease. Aim. To investigate whether a common V1062 LRP6 variant with similar functional consequences (nearly 5-foldlower signalling) was related to early carotid artery atherosclerosis (CAA) in hypertensive patients. Methods. Cross-sectional study of 273 hypertensive patients (age 1.3 mm) at the level of common, bifurcation and/or internal carotid arteries. Logistic regression models were used to estimate the independent effect of V1062 allele controlling for CAA established risk factors. Results. In our hypertensive patients, age, gender, dyslipidaemia, smoking habit, pulse pressure and CKD confirmed as risk fact ors for CAA. The V1062 LRP6 variant was a strong risk factor for CAA in both unadjusted (OR 1.75, 95%CI 1.02-3.02; p15% lumen reduction, class C and above following Taylor and Strandness) was considered, the results were also stronger (unadjusted OR 2.14, 95% CI1.2-3.84, p=0.011; adjusted OR 2.44, 95%CI 1.22-4.85, p=0.011). Conclusions. Beside the role of established risk factors, V1062 LRP6 variant and CAA are strongly associated in hypertensive patients, making LRP6 a novel interesting candidate gene for early coronary and carotid artery atherosclerosis.
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