A gene variant in the Atp10d gene associates with atherosclerotic indices in Japanese elderly population
A gene variant in the Atp10d gene associates with atherosclerotic indices in Japanese elderly population
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DOI：
10.1016/j.atherosclerosis.2013.08.034
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发表时间：
2013-11-01
期刊：
影响因子：
5.3
通讯作者：
Sawabe, Motoji
中科院分区：
文献类型：
--
作者：
Kengia, James Tumaini;Ko, Kyi Chan;Sawabe, Motoji
背景资料：ATP 10 D属于P型ATP酶亚家族，参与细胞生物膜的磷脂从细胞外质到细胞质小叶的移位。先前的全基因组关联研究（GWAS）发现Atp 10 d基因（rs 2351791）的一个变异与血脂谱和心肌梗死相关。本研究的目的是评估这种变异对日本老年人动脉粥样硬化的影响。方法：收集在JG-SNP研究中登记的连续尸检病例（n = 1536）。通过肉眼检查福尔马林固定的动脉，对样本进行动脉粥样硬化的病理学评估，并计算代表全身动脉的冠状动脉狭窄指数（CSI）、颅内动脉粥样硬化指数（ICAI）和病理性动脉粥样硬化指数（派）。结果：GG基因型的CSI和ICAI均显著高于GT基因型和TT基因型（p = 0.003和p = 0.001）;在调整年龄、高血压、糖尿病、HDL、吸烟和饮酒后，两种关联在次要等位基因显性模型中仍然显著（分别为p = 0.001和p = 0.001）。派与此变异无关。结论：日本老年人群Atp 10 d基因rs 2351791 SNP与心血管和颅内血管狭窄的易感性有关。(C)2013作者由Elsevier爱尔兰有限公司出版。保留所有权利。
Background: ATP10D belongs to a subfamily of P-type ATPases implicated in phospholipids translocation from the exoplasmic to the cytoplasmic leaflet of cellular biological membrane. Previous genome-wide association study (GWAS) identified that a variant in Atp10d gene (rs2351791) associates with serum lipid profile and myocardial infarction. The objective of this study is to assess the effect of this variant on atherosclerosis in Japanese elderly population.Method: Consecutive autopsy cases registered in JG-SNP study were recruited (n = 1536). The samples were pathologically assessed for atherosclerosis using macroscopic examination of the formalin-fixed arteries, and coronary stenotic index (CSI), intracranial atherosclerotic index (ICAI) and pathological atherosclerotic index (PAI), which represent systemic arteries were calculated. The variant rs2351791 (G/T) in Atp10d gene was genotyped by Taqman genotyping assay and association determined.Result: Both CSI and ICAI were significantly higher in GG genotype than GT genotype and TT genotype (p = 0.003 and p = 0.001, respectively). Both associations remained significant in minor allele dominant model after adjusting for age, hypertension, diabetes, HDL, smoking and drinking (p = 0.001 and p = 0.001, respectively). PAI was not associated with this variant. Consistent with the previous report, plasma HDL cholesterol level was lower in GG genotype compared to GT + TT genotypes (p = 0.001).Conclusion: The rs2351791 SNP in the Atp10d gene affects the susceptibility for cardiac and intracranial vascular stenosis in the elderly Japanese population. (C) 2013 The Authors. Published by Elsevier Ireland Ltd. All rights reserved.