Genetically elevated C-reactive protein and ischemic vascular disease
Genetically elevated C-reactive protein and ischemic vascular disease
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DOI：
10.1056/nejmoa0707402
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发表时间：
2008-10-30
影响因子：
158.5
通讯作者：
Nordestgaard, Borge G.
中科院分区：
文献类型：
--
作者：
Zacho, Jeppe;Tybjaerg-Hansen, Anne;Nordestgaard, Borge G.
背景资料：C-反应蛋白（CRP）水平升高与缺血性心脏病和缺血性脑血管病的风险增加有关。我们测试这是否是一个因果association.Methods：我们研究了10,276人从一般人群队列，其中包括1786人缺血性心脏病和741人缺血性脑血管疾病的发展。我们检查了另外31，992人的横断面一般人群研究，其中2521人患有缺血性心脏病，1483人患有缺血性脑血管病。最后，我们比较了2238例缺血性心脏病患者和4474例对照组，612例缺血性脑血管病患者和1224例对照组。我们测量了高灵敏度CRP的水平，并进行了基因分型的四个CRP多态性和两个载脂蛋白E polymorphism.Results：缺血性心脏病和缺血性脑血管疾病的风险分别增加了1.6和1.3倍，在CRP水平高于3毫克每升的人，相比，CRP水平低于1毫克每升的人。四种CRP多态性的基因型组合与CRP水平升高高达64%相关，导致理论预测缺血性心脏病风险增加高达32%，缺血性脑血管病风险增加高达25%。然而，这些基因型组合与缺血性血管疾病的风险增加无关。相比之下，载脂蛋白E基因型与胆固醇水平升高和缺血性心脏病的风险增加。结论：CRP基因多态性与CRP水平显着增加，从而与理论预测的缺血性血管疾病的风险增加。然而，这些多态性本身并不与缺血性血管疾病的风险增加相关。
Background: Elevated levels of C-reactive protein (CRP) are associated with increased risks of ischemic heart disease and ischemic cerebrovascular disease. We tested whether this is a causal association.Methods: We studied 10,276 persons from a general population cohort, including 1786 in whom ischemic heart disease developed and 741 in whom ischemic cerebrovascular disease developed. We examined another 31,992 persons from a cross-sectional general population study, of whom 2521 had ischemic heart disease and 1483 had ischemic cerebrovascular disease. Finally, we compared 2238 patients with ischemic heart disease with 4474 control subjects and 612 patients with ischemic cerebrovascular disease with 1224 control subjects. We measured levels of high-sensitivity CRP and conducted genotyping for four CRP polymorphisms and two apolipoprotein E polymorphisms.Results: The risk of ischemic heart disease and ischemic cerebrovascular disease was increased by a factor of 1.6 and 1.3, respectively, in persons who had CRP levels above 3 mg per liter, as compared with persons who had CRP levels below 1 mg per liter. Genotype combinations of the four CRP polymorphisms were associated with an increase in CRP levels of up to 64%, resulting in a theoretically predicted increased risk of up to 32% for ischemic heart disease and up to 25% for ischemic cerebrovascular disease. However, these genotype combinations were not associated with an increased risk of ischemic vascular disease. In contrast, apolipoprotein E genotypes were associated with both elevated cholesterol levels and an increased risk of ischemic heart disease.Conclusions: Polymorphisms in the CRP gene are associated with marked increases in CRP levels and thus with a theoretically predicted increase in the risk of ischemic vascular disease. However, these polymorphisms are not in themselves associated with an increased risk of ischemic vascular disease.