A single nucleotide polymorphism in exon 3 of the kallikrein 1 gene is associated with large but not small abdominal aortic aneurysm
A single nucleotide polymorphism in exon 3 of the kallikrein 1 gene is associated with large but not small abdominal aortic aneurysm
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DOI：
10.1016/j.atherosclerosis.2011.04.017
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发表时间：
2011-08-01
期刊：
影响因子：
5.3
通讯作者：
Golledge, Jonathan
中科院分区：
文献类型：
--
作者：
Biros, Erik;Norman, Paul E.;Golledge, Jonathan
目的：腹主动脉瘤（AAA）是一种迟发性退行性疾病，其遗传成分被认为是由多种风险等位基因引起的。染色体 19q13 上的一个基因座先前已被认为与 AAA 相关。编码激肽释放酶 1 (KLK1) 的基因位于染色体 19q13 上，单核苷酸多态性 (SNP) rs5516 先前已被证明会导致 KLK1 转录调控区的结构变化。本研究的目的是调查 rs5516 是否与 AAA 和主动脉直径相关。 方法：我们对来自西澳大利亚 (n = 1304) 和昆士兰州 (n = 325) 的两个独立受试者组进行了病例对照研究，其中分别有 609 名和 225 名患有 AAA。此外，我们分析了从 12 名接受 AAA 手术的患者和 6 名器官捐献者的腹主动脉活检中提取的 RNA。结果：在调整其他危险因素后，在西澳大利亚男性中使用显性模型，在昆士兰受试者中使用隐性模型，rs5516 多态性的 G 等位基因与大而不是小 AAA 相关。在患有大 AAA 的受试者中，G 等位基因与主动脉直径相关。与对照活检相比，KLK1 的短剪接变体在 AAA 中表达上调。结论：这项研究表明，KLK1 的遗传多态性可能会增加发生晚期 AAA 的风险。 (C) 2011 Elsevier Ireland Ltd. 保留所有权利。
Objective: Abdominal aortic aneurysm (AAA) is a late onset degenerative condition with an inherited component thought to be due to multiple risk alleles. A locus on chromosomes 19q13 has been previously associated with AAA. The gene encoding kallikrein 1 (KLK1) is located on chromosome 19q13 and the single nucleotide polymorphism (SNP) rs5516 has been previously shown to lead to structural changes in the KLK1 transcription regulatory region. The aim of this study was to investigate whether rs5516 was associated with AAA and aortic diameter.Methods: We performed a case-control study on two independent subject groups from Western Australia (n = 1304) and Queensland (n = 325) of which 609 and 225 had an AAA, respectively. In addition, we analysed RNA extracted from abdominal aortic biopsies from 12 patients undergoing AAA surgery and 6 organ donors.Results: After adjusting for other risk factors the G allele of the rs5516 polymorphism was associated with large but not small AAA using a dominant model in the Western Australian men and a recessive model in Queensland subjects. In subjects with large AAA the G allele was associated with aortic diameter. The short splice variant of KLK1 was upregulated within AAA compared to control biopsies.Conclusion: This study suggests that a genetic polymorphism in KLK1 may contribute to the risk of developing later stage AAA. (C) 2011 Elsevier Ireland Ltd. All rights reserved.