基质Gla蛋白的常见基因变异与动脉壁钙化有关，但与动脉粥样硬化斑块中的钙化无关。
Common genetic variants of MGP are associated with calcification on the arterial wall but not with calcification present in the atherosclerotic plaques.
作者信息
Wang Yibo, Chen Jinxing, Zhang Yu, Yu Weifeng, Zhang Channa, Gong Ling, Shao Liying, Lu Jinguo, Gao Yang, Chen Xuannan, Chen Xi, Hui Rutai
机构信息
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.
出版信息
Circ Cardiovasc Genet. 2013 Jun;6(3):271-8. doi: 10.1161/CIRCGENETICS.113.000003.
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.
METHODS AND 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.
背景
动脉钙化有两种内表型，即动脉壁钙化和动脉粥样硬化斑块钙化，它们与不同类型的心血管事件相关。基质Gla蛋白（MGP）缺乏的小鼠显示，MGP与无动脉粥样硬化斑块的动脉壁钙化密切相关，且MGP变异与心肌梗死无显著关联。MGP可能在这两种内表型中发挥不同作用。
方法与结果
我们分析了MGP变异体rs4236、rs1800801和rs1800802与通过多排螺旋CT血管造影确定的两种内表型之间的关联。共纳入585例冠状动脉壁钙化患者、675例冠状动脉粥样硬化斑块钙化患者、454例主动脉壁钙化患者及725例对照者。经Bonferroni校正后，rs4236和rs1800801仍与动脉壁钙化相关，在冠状动脉壁钙化中，rs4236的比值比为0.708（95%置信区间为0.540 - 0.928），rs1800801的比值比为0.652（95%置信区间为0.479 - 0.888）；在主动脉壁钙化中，rs4236的比值比为0.699（95%置信区间为0.525 - 0.931），rs1800801的比值比为0.650（95%置信区间为0.467 - 0.905）。这些变异与冠状动脉壁钙化的钙化严重程度（通过ln（CAC阿加特斯顿积分 + 1））相关，但与动脉粥样硬化斑块钙化无关。根据它们与动脉壁钙化的关联，rs4236C和rs1800801A与正常对照者中较高的MGP血浆水平相关，而rs1800802C与较低的MGP水平相关。由于钙化在斑块易损性中的作用，我们还在771例对照者和752例患者中确定了它们与急性心肌梗死的关联，未发现相关性。
结论
MGP基因变异与动脉壁钙化相关，但与动脉粥样硬化斑块钙化无关。
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