Carotid artery atherosclerosis in hypertensive patients with a functional LDL receptor-related protein 6 gene variant

• Published in: Nutrition, metabolism, and cardiovascular diseases Vol. 21; no. 2; pp. 150 - 156
• Main Authors: Sarzani, R, Salvi, F, Bordicchia, M, Guerra, F, Battistoni, I, Pagliariccio, G, Carbonari, L, Dessì-Fulgheri, P, Rappelli, A
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2011
• Subjects: Adult; alleles; atherosclerosis; beta Catenin - genetics; beta Catenin - metabolism; Cardiovascular; carotid arteries; Carotid Artery Diseases - genetics; Carotid Artery Diseases - metabolism; Carotid atherosclerosis; coronary artery disease; fasting; Female; Gene Expression; Genetics; genotype; glomerular filtration rate; glucose; Humans; hyperlipidemia; Hypertension; Hypertension - genetics; Hypertension - metabolism; LDL-Receptor Related Proteins - genetics; LDL-Receptor Related Proteins - metabolism; Lipoprotein receptor-related protein 6; Logistic Models; low density lipoprotein; Low Density Lipoprotein Receptor-Related Protein-6; Male; Middle Aged; noninsulin-dependent diabetes mellitus; patients; Plaque, Atherosclerotic - metabolism; regression analysis; Retrospective Studies; Risk Factors; Signal Transduction; smoking (habit); ultrasonography; Wnt Proteins - genetics; Wnt Proteins - metabolism; Wnt/β-catenin; Hypertension; Genetics; Carotid atherosclerosis; Lipoprotein receptor-related protein 6; Wnt/β-catenin
• ISSN: 0939-4753; 1590-3729
• DOI: 10.1016/j.numecd.2009.08.004

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 ≥1.3 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 = 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.