title: Coronary Artery Calcification and Rheumatoid Arthritis: Lack of Relationship to Risk Alleles for Coronary Artery Disease in the General Population.
abstract: Coronary artery disease (CAD) in the general population is characterized by an increased frequency of particular susceptibility single-nucleotide polymorphisms (SNPs). Because the frequency of CAD is increased among patients with rheumatoid arthritis (RA), we sought to determine whether the frequency of these SNPs is increased in RA patients with CAD, hypothesizing that RA could enhance CAD risk by acting through established genetic pathways predisposing to CAD.
  
  
  
  Coronary artery calcification (CAC) as detected by computed tomography was used as a measure of CAD in 561 patients with RA. One hundred SNPs associated with CAD in the general population were genotyped or imputed, and their relationship to CAC was established through multiple regression analysis for individual SNPs and a genetic risk score representing their cumulative effect.
  
  
  
  Ninety-one CAD-related SNPs were genotyped successfully; of these, 81 exhibited no association with CAC (Agatston units) or different CAC categorizations, either individually or collectively, in the genetic risk score. Only rs579459 (ABO) and rs17676451 (HAL) had a consistent positive association between genotype and CAC, with a significant increase in the frequency of the effect allele in both homozygous and heterozygous genotype distributions. Five were variably negatively associated. Furthermore, a positive association between the Disease Activity Score in 28 joints and CAC was observed, and after adjustment for traditional cardiovascular risk factors, it was not modified by correcting for the CAD-related SNP genetic risk score.
  
  
  
  The increased risk of CAC in patients with RA does not appear to operate primarily through established genetically regulated atherogenic mechanisms that are preponderant in the general population.
authors.affiliation: Hospital Universitario de Canarias, Tenerife, Spain.
authors.forename: Iván
authors.identifier: 0000-0003-0197-5267
authors.initials: I
authors.lastname: Ferraz-Amaro
authors.affiliation: Columbia University, New York, New York.
authors.forename: Robert
authors.initials: R
authors.lastname: Winchester
authors.affiliation: The Feinstein Institute for Medical Research, Manhasset, New York.
authors.forename: Peter K
authors.initials: PK
authors.lastname: Gregersen
authors.affiliation: University of Alabama at, Birmingham.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Reynolds
authors.affiliation: West Penn Allegheny Health System, Pittsburgh, Pennsylvania, and Temple University School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Mary Chester
authors.initials: MC
authors.lastname: Wasko
authors.affiliation: Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Anette
authors.initials: A
authors.lastname: Oeser
authors.affiliation: Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Cecilia P
authors.initials: CP
authors.lastname: Chung
authors.affiliation: Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: C Michael
authors.initials: CM
authors.lastname: Stein
authors.affiliation: Columbia University, New York, New York.
authors.forename: Jon T
authors.initials: JT
authors.lastname: Giles
authors.affiliation: Columbia University, New York, New York.
authors.forename: Joan M
authors.initials: JM
authors.lastname: Bathon
mesh_terms: D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D003324:Coronary Artery Disease / Q000150:complications* / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D061205:Vascular Calcification / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*