title: Increased carotid artery intima-media thickness is associated with a novel mutation of low-density lipoprotein receptor independently of major cardiovascular risk factors.
abstract: 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.
authors: Department of Clinical and Experimental Medicine, Ceinge, Italy. pauciull@unina.it
authors: Paolo
authors: P
authors: Pauciullo
authors: Alessandro
authors: A
authors: Giannino
authors: Mario
authors: M
authors: De Michele
authors: Marco
authors: M
authors: Gentile
authors: Rosario
authors: R
authors: Liguori
authors: Anagnostis
authors: A
authors: Argiriou
authors: Alessandra
authors: A
authors: Carlotto
authors: Fulvio
authors: F
authors: Faccenda
authors: Mario
authors: M
authors: Mancini
authors: M Gene
authors: MG
authors: Bond
authors: Vincenzo
authors: V
authors: De Simone
authors: Paolo
authors: P
authors: Rubba
mesh_terms: D000293:Adolescent; D000328:Adult; D001161:Arteriosclerosis / Q000235:genetics / Q000473:pathology; D002318:Cardiovascular Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology*; D002648:Child; D002784:Cholesterol / Q000097:blood; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004452:Echocardiography; D004777:Environment; D005247:Feeding Behavior; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000000981:diagnostic imaging / Q000235:genetics; D008019:Life Style; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics* / Q000502:physiology*; D011973:Receptors, LDL / Q000235:genetics*; D012307:Risk Factors; D013710:Tendons / Q000473:pathology; D014973:Xanthomatosis / Q000473:pathology
chemical_list: D018076:DNA, Complementary; D011973:Receptors, LDL; D002784:Cholesterol