Genetic loci for coronary calcification and serum lipids relate to aortic and carotid calcification

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

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)47-53
Number of pages7
JournalCirculation : Cardiovascular Genetics
Volume6
Issue number1
DOIs
Publication statusPublished - Feb 2013
Externally publishedYes

Keywords

  • Aged
  • Aorta, Thoracic/diagnostic imaging
  • Atherosclerosis/diagnostic imaging
  • Calcinosis/complications
  • Carotid Arteries/diagnostic imaging
  • Cohort Studies
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Humans
  • Lipids/blood
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Risk Factors
  • Tomography, X-Ray Computed

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