Increased carotid artery intima-media thickness is associated with a novel mutation of low-density lipoprotein receptor independently of major cardiovascular risk factors

• Published in: Metabolism, clinical and experimental Vol. 52; no. 11; pp. 1433 - 1438
• Main Authors: Pauciullo, Paolo, Giannino, Alessandro, De Michele, Mario, Gentile, Marco, Liguori, Rosario, Argiriou, Anagnostis, Carlotto, Alessandra, Faccenda, Fulvio, Mancini, Mario, Bond, M.Gene, De Simone, Vincenzo, Rubba, Paolo
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.11.2003; Elsevier
• Subjects: Adolescent; Adult; Arteriosclerosis - genetics; Arteriosclerosis - pathology; Biological and medical sciences; Cardiology. Vascular system; Cardiovascular Diseases - diagnostic imaging; Cardiovascular Diseases - genetics; Cardiovascular Diseases - pathology; Carotid Arteries - diagnostic imaging; Carotid Arteries - pathology; Child; Cholesterol - blood; Coronary heart disease; Disorders of blood lipids. Hyperlipoproteinemia; DNA, Complementary - biosynthesis; DNA, Complementary - genetics; Echocardiography; Environment; Feeding Behavior; Female; Heart; Humans; Hyperlipoproteinemia Type II - diagnostic imaging; Hyperlipoproteinemia Type II - genetics; Life Style; Male; Medical sciences; Metabolic diseases; Middle Aged; Mutation - genetics; Mutation - physiology; Receptors, LDL - genetics; Risk Factors; Tendons - pathology; Xanthomatosis - pathology; Human; Media; Cardiovascular disease; Metabolic diseases; Lipids; Receiver; Hyperlipoproteinemia; Coronary heart disease; Genetic determinism; Thickness; Lipoprotein LDL; Familial disease; Association; Hypercholesterolemia; Carotid; Risk factor; Intima; Mutation; Dyslipemia
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/S0026-0495(03)00255-5

The current study sought to investigate the role of low-density lipoprotein receptor (LDLr) mutations in assessing the risk profile of familial hypercholesterolemia (FH) patients, independently of major cardiovascular risk factors. FH due to LDLr mutations is associated with premature atherosclerosis. The variable clinical severity of the disease in heterozygotes has been related to cholesterol levels and the coexistence of other cardiovascular risk factors, but the independent role of different LDLr mutations is still unclear. cDNA of LDL gene was sequenced in 102 patients with clinical features of heterozygous FH. Carotid artery intima-media thickness (IMT) was measured by B-mode ultrasound imaging in all patients. Sixteen different mutations (5 never described) were found in 82 patients (49 families; mean age, 39 years; 53% women). One of the newly described mutations, the 2312-3 C→A, was found in 24 patients (13 families). The mean of maximum thicknesses was significantly higher in the 2312-3 C→A group than in patients with other LDLr mutations (P = .004 after adjustment for major cardiovascular risk factors). Similar results (P = .001) were obtained in the adjusted comparisons of probands only, and of the patients with similar baseline cholesterol (P = .002). This study indicates that the identification of an LDLr mutation can help to assess the risk profile of FH patients independently of the major cardiovascular risk factors.