Candidate gene association study of coronary artery calcification in chronic kidney disease: findings from the CRIC study (Chronic Renal Insufficiency Cohort). Academic Article Article uri icon

Overview

MeSH

  • Adult
  • African Continental Ancestry Group
  • Aged
  • Cohort Studies
  • European Continental Ancestry Group
  • Female
  • Genome-Wide Association Study
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors

MeSH Major

  • Coronary Vessels
  • Myocardial Infarction
  • Polymorphism, Single Nucleotide
  • Renal Insufficiency, Chronic
  • Vascular Calcification

abstract

  • This study sought to identify loci for coronary artery calcification (CAC) in patients with chronic kidney disease (CKD). CKD is associated with increased CAC and subsequent coronary heart disease (CHD), but the mechanisms remain poorly defined. Genetic studies of CAC in CKD may provide a useful strategy for identifying novel pathways in CHD. We performed a candidate gene study (∼2,100 genes; ∼50,000 single nucleotide polymorphisms [SNPs]) of CAC within the CRIC (Chronic Renal Insufficiency Cohort) study (N = 1,509; 57% European, 43% African ancestry). SNPs with preliminary evidence of association with CAC in CRIC were examined for association with CAC in the PennCAC (Penn Coronary Artery Calcification) (N = 2,560) and AFCS (Amish Family Calcification Study) (N = 784) samples. SNPs with suggestive replication were further analyzed for association with myocardial infarction (MI) in the PROMIS (Pakistan Risk of Myocardial Infarction Study) (N = 14,885). Of 268 SNPs reaching p < 5 × 10(-4) for CAC in CRIC, 28 SNPs in 23 loci had nominal support (p < 0.05 and in same direction) for CAC in PennCAC or AFCS. Besides chr9p21 and COL4A1, known loci for CHD, these included SNPs having reported genome-wide association study association with hypertension (e.g., ATP2B1). In PROMIS, 4 of the 23 suggestive CAC loci (chr9p21, COL4A1, ATP2B1, and ABCA4) had significant associations with MI, consistent with their direction of effect on CAC. We identified several loci associated with CAC in CKD that also relate to MI in a general population sample. CKD imparts a high risk of CHD and may provide a useful setting for discovery of novel CHD genes and pathways. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

authors

publication date

  • August 27, 2013

has subject area

  • Adult
  • African Continental Ancestry Group
  • Aged
  • Cohort Studies
  • Coronary Vessels
  • European Continental Ancestry Group
  • Female
  • Genome-Wide Association Study
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Renal Insufficiency, Chronic
  • Risk Factors
  • Vascular Calcification

Research

keywords

  • Journal Article
  • Multicenter Study

Identity

Language

  • eng

PubMed Central ID

  • PMC3953823

Digital Object Identifier (DOI)

  • 10.1016/j.jacc.2013.01.103

PubMed ID

  • 23727086

Additional Document Info

start page

  • 789

end page

  • 798

volume

  • 62

number

  • 9