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Genetics of Aortic and Carotid Calcification: The Role of Serum Lipids

Posted in Abdominal Aorta, Atherogenic Processes & Pathology, Biological Networks, Gene Regulation and Evolution, Cardiovascular Pharmacogenomics, Carotid Artery, Cerebrovascular and Neurodegenerative Diseases, Chemical Biology and its relations to Metabolic Disease, Chemical Genetics, Computational Biology/Systems and Bioinformatics, Frontiers in Cardiology and Cardiovascular Disorders, Genome Biology, Medical and Population Genetics, Origins of Cardiovascular Disease, Peripheral Arterial Disease & Peripheral Vascular Surgery, Personalized and Precision Medicine & Genomic Research, Pharmacogenomics, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Thoracic Aorta, tagged , , , , on December 12, 2013| Leave a Comment »

Genetics of Aortic and Carotid Calcification: The Role of Serum Lipids

Reporter: Aviva Lev-Ari, PhD, RN

Genetic Loci for Coronary Calcification and Serum Lipids Relate to Aortic and Carotid Calcification

Daniel Bos, MD, M. Arfan Ikram, MD, PhD, Aaron Isaacs, PhD, Benjamin F.J. Verhaaren, MD, Albert Hofman, MD, PhD, Cornelia M. van Duijn, PhD, Jacqueline C.M. Witteman, PhD, Aad van der Lugt, MD, PhD and Meike W. Vernooij, MD, PhD

Author Affiliations

From the Departments of Radiology (D.B., M.A.I., B.F.J.V., A.v.d.L., M.W.V), Epidemiology (D.B., M.A.I., A.I., B.F.J.V., A.H., C.M.v.D., J.C.M.W., M.W.V.), and Genetic Epidemiology Unit (A.I., C.M.v.D.), Erasmus MC, Rotterdam, the Netherlands.

Correspondence to Meike W. Vernooij, MD, PhD, Department of Radiology, Erasmus MC, Gravendijkwal 230, PO Box 2040, 3000CA Rotterdam, the Netherlands. E-mailm.vernooij@erasmusmc.nl

Abstract

Background—Atherosclerosis in different vessel beds shares lifestyle and environmental risk factors. It is unclear whether this holds for genetic risk factors. Hence, for the current study genetic loci for coronary artery calcification and serum lipid levels, one of the strongest risk factors for atherosclerosis, were used to assess their relation with atherosclerosis in different vessel beds.

Methods and Results—From 1987 persons of the population-based Rotterdam Study, 3 single-nucleotide polymorphisms (SNPs) for coronary artery calcification and 132 SNPs for total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides were used. To quantify atherosclerotic calcification as a marker of atherosclerosis, all participants underwent nonenhanced computed tomography of the aortic arch and carotid arteries. Associations between genetic risk scores of the joint effect of the SNPs and of all calcification were investigated. The joint effect of coronary artery calcification–SNPs was associated with larger calcification volumes in all vessel beds (difference in calcification volume per SD increase in genetic risk score: 0.15 [95% confidence interval, 0.11–0.20] in aorta, 0.14 [95% confidence interval, 0.10–0.18] in extracranial carotids, and 0.11 [95% confidence interval, 0.07–0.16] in intracranial carotids). The joint effect of total cholesterol SNPs, low-density lipoprotein SNPs, and of all lipid SNPs together was associated with larger calcification volumes in both the aortic arch and the carotid arteries but attenuated after adjusting for the lipid fraction and lipid-lowering medication.

Conclusions—The genetic basis for aortic arch and carotid artery calcification overlaps with the most important loci of coronary artery calcification. Furthermore, serum lipids share a genetic predisposition with both calcification in the aortic arch and the carotid arteries, providing novel insights into the cause of atherosclerosis.

 SOURCE:

Circulation: Cardiovascular Genetics.2013; 6: 47-53

Published online before print December 16, 2012,

doi: 10.1161/ CIRCGENETICS.112.963934

 

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