Hornstrup Louise S, Tybjærg-Hansen Anne, Haase Christiane L, Nordestgaard Børge G, Sillesen Henrik, Grande Peer, Frikke-Schmidt Ruth
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
Circ Cardiovasc Genet. 2011 Oct;4(5):534-41. doi: 10.1161/CIRCGENETICS.110.958801. Epub 2011 Aug 10.
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.
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.
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.
弹性假黄瘤（PXE）是一种常染色体隐性疾病，由ABCC6功能丧失性突变引起，其特征为弹性组织钙化，进而导致皮肤、眼部和缺血性血管疾病。正如先前研究表明杂合子患缺血性心脏病（IHD）的风险为4至11倍，我们检验了如下假设：在白种人中最常见的导致PXE的R1141X突变的杂合性与缺血性血管疾病风险相关。
我们研究了来自普通人群的10276人，其中包括1985例IHD患者和989例缺血性脑血管疾病（ICVD）患者。我们检查了来自一项横断面普通人群研究的45603人，其中3738例患有IHD，2335例患有ICVD。最后，我们将4851例IHD患者和625例ICVD患者分别与4851例和625例匹配的对照者进行比较。我们对所有研究中的参与者进行ABCC6 R1141X基因分型。在所研究的所有人群中，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基因型在最大终点事件IHD的风险上与年龄不存在交互作用。最后，在普通人群中，R1141X基因型与高敏C反应蛋白、纤维蛋白原、血压或脂质及脂蛋白的血浆水平变化无关。
在包括66831名参与者和13642例缺血性血管事件病例的4项研究中，ABCC6 R1141X杂合性与IHD、心肌梗死、ICVD或缺血性中风风险无关。
