Common variants in the periostin gene influence development of atherosclerosis in young persons.
Common variants in the periostin gene influence development of atherosclerosis in young persons.
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DOI：
10.1161/atvbaha.111.224352
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发表时间：
2011-07
期刊：
影响因子：
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通讯作者：
Herrington D
中科院分区：
文献类型：
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作者：
Hixson JE;Shimmin LC;Montasser ME;Kim DK;Zhong Y;Ibarguen H;Follis J;Malcom G;Strong J;Howard T;Langefeld C;Liu Y;Rotter JI;Johnson C;Herrington D
我们研究了编码骨膜蛋白（POSTN）的基因中的遗传变异（罕见和常见）对动脉粥样硬化的影响，这是在“青年动脉粥样硬化的病理生物学决定因素”研究（PDAY）的动脉标本中测量的。对PDAY受试者（n= 2，527）中常见的POR4变体（87个SNP）进行了全面调查，确定了许多与腹主动脉隆起病变和胸主动脉脂肪条纹相关的SNP。这些SNP属于跨越整个基因座的少数相关箱。为了检查罕见变异的影响，我们对有凸起病变的PDAY病例（n=291）和无凸起病变的对照（n=294）的PORYSTs功能区进行了重新测序。然而，我们使用加权求和法进行罕见变异分析，未发现与病例对照状态有显著相关性。我们在PDAY研究中发现了与年轻人动脉病变相关的POR4常见变异。这一发现有力地支持了骨膜蛋白在动脉粥样硬化形成中的作用，正如最近的蛋白质组学分析所表明的那样，发现骨膜蛋白在动脉粥样硬化病变中大量表达。遗传变异可能会通过已知的骨膜蛋白参与多种相关途径（包括血管生成、血管重塑以及刺激血管平滑肌细胞的迁移和分化）来影响动脉粥样硬化。
We investigated the influence of genetic variants (rare and common) in the gene encoding periostin (POSTN) on atherosclerosis as measured in arterial specimens from the “Pathobiological Determinants of Atherosclerosis in Youth” study (PDAY). A comprehensive survey of common POSTN variants (87 SNPs) in PDAY subjects (n=2,527) identified numerous SNPs associated with raised lesions in abdominal aorta, and with fatty streaks in thoracic aorta. These SNPs belonged to a small number of correlation bins that spanned the entire locus. To examine effects of rare variants, we resequenced POSTN functional regions in PDAY cases with raised lesions (n=291) and controls with no raised lesions (n=294). However, we found no significant associations with case-control status for carriers of POSTN rare variants using the Weighted Sum Method for rare variant analysis. We identified common variants in POSTN that are associated with arterial lesions in young persons from the PDAY study. This finding strongly supports a role for periostin in atherogenesis, as suggested by recent proteomics analysis that found abundant expression of periostin in atherosclerotic lesions. Genetic variation may influence atherosclerosis via periostin’s known involvement in multiple relevant pathways including angiogenesis, vascular remodeling, and stimulation of migration and differentiation of vascular smooth muscle cells.