The risk of tendon xanthomas in familial hypercholesterolaemia is influenced by variation in genes of the reverse cholesterol transport pathway and the low-density lipoprotein oxidation pathway

• Published in: European heart journal Vol. 31; no. 8; pp. 1007 - 1012
• Main Authors: Oosterveer, Daniëlla M., Versmissen, Jorie, Yazdanpanah, Mojgan, Defesche, Joep C., Kastelein, John J.P., Sijbrands, Eric J.G.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.04.2010
• Subjects: Adult; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cholesterol - genetics; Disorders of blood lipids. Hyperlipoproteinemia; Familial hypercholesterolaemia; Female; Genotype; Humans; Hyperlipoproteinemia Type II - genetics; LDL oxidation; Lipoproteins, LDL - genetics; Lipoproteins, LDL - metabolism; Male; Medical sciences; Membrane Transport Proteins - genetics; Metabolic diseases; Middle Aged; Oxidation-Reduction; Polymorphism, Single Nucleotide - genetics; Reverse cholesterol transport; Risk Factors; Tendinopathy - genetics; Xanthomas; Xanthomatosis - genetics; Skin disease; Xanthoma; Reverse cholesterol transport; Variations; Cardiovascular disease; Lipids; Risk; Hyperlipoproteinemia; Density; Vascular disease; Lipoprotein LDL; Gene; Atherosclerosis; Oxidation; Benign neoplasm; Dyslipemia; Cardiology; Familial hypercholesterolaemia; LDL oxidation; Metabolic diseases; Xanthomas; Cholesterol; Genetic disease; Hypercholesterolemia; Low; Risk factor; Circulatory system; Transport; Tendon
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1093/eurheartj/ehp538

Aims The presence of tendon xanthomas is a marker of high risk of cardiovascular disease (CVD) among patients with familial hypercholesterolaemia (FH). Therefore, xanthomas and atherosclerosis may result from the same pathophysiological mechanisms. Reverse cholesterol transport (RCT) and low-density lipoprotein (LDL) oxidation are pathophysiological pathways of atherosclerosis, and it is well established that genetic variation in these pathways influences CVD risk. We therefore determined whether genetic variation in these pathways is also associated with the occurrence of tendon xanthomas in FH patients. Methods and results Four genetic variants in each pathway were genotyped in 1208 FH patients. We constructed a gene-load score for both pathways. The odds of xanthomas increased with the number of the risk alleles in the RCT pathway (OR 1.21, 95% CI 1.08–1.36, Ptrend = 0.0014). Similarly, higher numbers of risk alleles in the LDL oxidation pathway were associated with the presence of xanthomas (OR 1.24, 95% CI 1.08–1.41, Ptrend = 0.0015). Conclusion The presence of tendon xanthomas in FH patients is associated with genetic variation in the RCT and LDL oxidation pathways. These results support the hypothesis that xanthomas and atherosclerosis share pathophysiological mechanisms.