title: Common genetic variants of MGP are associated with calcification on the arterial wall but not with calcification present in the atherosclerotic plaques.
abstract: BACKGROUND
  Two endophenotypes of arterial calcification, calcification on arterial wall and calcification in atherosclerotic plaques, are associated with different types of cardiovascular events. Mgp-deficient mice showed matrix Gla protein (MGP) is strongly associated with calcification on arterial wall without atherosclerotic plaques, and MGP variants were not significantly associated with myocardial infarction. MGP may play different roles in the 2 endophenotypes.
  
  
  RESULTS
  We analyzed the associations of MGP variants rs4236, rs1800801, and rs1800802 with the 2 endophenotypes determined by multidetector computed tomography angiography. A total of 585 with calcification on coronary artery wall, 675 with calcification in coronary atherosclerotic plaques, 454 with calcification on aortic wall, and 725 controls were enrolled. After Bonferroni correction, rs4236 and rs1800801 were still associated with calcification on arterial wall, the odds ratios were 0.708 (95% confidence interval, 0.540-0.928) for rs4236 and 0.652 (95% confidence interval, 0.479-0.888) for rs1800801 in coronary artery wall calcification, and 0.699 (95% confidence interval, 0.525-0.931) for rs4236 and 0.650 (95% confidence interval, 0.467-0.905) for rs1800801 in aortic wall calcification, respectively. The variants were correlated with calcification severity by ln(CAC Agatston score+1) in coronary artery wall calcification but not in atherosclerotic plaque calcification. In accordance with their associations with calcification on arterial wall, rs4236C and rs1800801A were associated with higher MGP plasma levels, whereas rs1800802C was associated with lower MGP levels in normal controls. Because of the role of calcification in plaque vulnerability, their associations with acute myocardial infarction were also determined in 771 controls and 752 patients, no association was found.
  
  
  CONCLUSIONS
  MGP genetic variants showed association with calcification on arterial wall but not with calcification in atherosclerotic plaques.
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Sino-German Laboratory for Molecular Medicine, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. yibowang@hotmail.com
authors.forename: Yibo
authors.initials: Y
authors.lastname: Wang
authors.forename: Jinxing
authors.initials: J
authors.lastname: Chen
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Weifeng
authors.initials: W
authors.lastname: Yu
authors.forename: Channa
authors.initials: C
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Gong
authors.forename: Liying
authors.initials: L
authors.lastname: Shao
authors.forename: Jinguo
authors.initials: J
authors.lastname: Lu
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.forename: Xuannan
authors.initials: X
authors.lastname: Chen
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Rutai
authors.initials: R
authors.lastname: Hui
mesh_terms: D000368:Aged; D000818:Animals; D002114:Calcinosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D009202:Cardiomyopathies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D000097568:Matrix Gla Protein
chemical_list: D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D000097568:Matrix Gla Protein