Heterozygosity for R1141X in ABCC6 and Risk of Ischemic Vascular Disease
Heterozygosity for R1141X in ABCC6 and Risk of Ischemic Vascular Disease
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DOI：
10.1161/circgenetics.110.958801
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发表时间：
2011-10-01
影响因子：
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通讯作者：
Frikke-Schmidt, Ruth
中科院分区：
文献类型：
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作者：
Hornstrup, Louise S.;Tybjaerg-Hansen, Anne;Frikke-Schmidt, Ruth
背景-弹性假黄瘤（PXE）是一种由 ABCC6 功能丧失突变引起的常染色体隐性遗传疾病，其特征是弹性钙化，导致皮肤、眼部和缺血性血管疾病。我们测试了这样的假设：R1141X（白种人中最常见的引起 PXE 的突变）的杂合性与缺血性血管疾病的风险相关，因为之前的研究表明杂合子患缺血性心脏病 (IHD) 的风险高出 4 至 11 倍。 方法和结果 - 我们研究了普通人群中的 10 276 人，其中包括 1985 名患有 IHD 的人和 989 名患有缺血性心脏病的人。脑血管疾病（ICVD）。我们对来自一项横断面一般人群研究的 45,603 人进行了检查，其中 3738 人患有 IHD，2335 人患有 ICVD。最后，我们将 4851 名 IHD 患者和 625 名 ICVD 患者分别与 4851 名和 625 名匹配的对照受试者进行了比较。我们对所有研究中的参与者进行了 ABCC6 R1141X 的基因分型。在所有研究人群中，R1141X 的频率为 0.6%。 ABCC6 R1141X 基因型与 IHD、心肌梗死、ICVD 或缺血性中风风险增加无关。此外，R1141X 基因型在最大终点 IHD 的风险上与年龄没有相互作用。最后，R1141X 基因型与一般人群中高敏 C 反应蛋白、纤维蛋白原、血压或血脂和脂蛋白血浆水平的变化无关。结论 - 在 4 项研究中，包括 66 831 名参与者和 13 642 例缺血性血管事件病例，ABCC6 R1141X 杂合性与 IHD、心肌梗死、ICVD 风险无关。或缺血性中风。 （Circ Cardiovasc Genet。2011；4：534-541。）
Background-Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease caused by loss-of-function mutations in ABCC6 and characterized by elastic calcification leading to dermal, ocular, and ischemic vascular disease. We tested the hypothesis that heterozygosity for R1141X, the most frequent PXE-causing mutation in Caucasians, associated with risk of ischemic vascular disease, as previous studies suggested 4- to 11-fold risk of ischemic heart disease (IHD) in heterozygotes.Methods and Results-We studied 10 276 persons from the general population, including 1985 with IHD and 989 with ischemic cerebrovascular disease (ICVD). We examined 45 603 individuals from a cross-sectional general population study, of whom 3738 had IHD and 2335 had ICVD. Finally, we compared 4851 patients with IHD and 625 patients with ICVD with, respectively, 4851 and 625 matched control subjects. We genotyped participants in all studies for ABCC6 R1141X. The frequency of R1141X was 0.6% in all populations studied. ABCC6 R1141X genotype was not associated with an increased risk of IHD, myocardial infarction, ICVD, or ischemic stroke. Furthermore, R1141X genotype did not interact with age on risk of the largest end point, IHD. Finally, R1141X genotype did not associate with variation in plasma levels of high-sensitivity C-reactive protein, fibrinogen, blood pressure, or lipid and lipoproteins in the general population.Conclusions-In 4 studies including 66 831 participants and 13 642 cases with ischemic vascular events, heterozygosity for ABCC6 R1141X did not associate with risk of IHD, myocardial infarction, ICVD, or ischemic stroke. (Circ Cardiovasc Genet. 2011; 4:534-541.)