UvA-DARE ( Digital Academic Repository ) Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis
UvA-DARE ( Digital Academic Repository ) Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis
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2009
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通讯作者：
A. Schaefer;G. Richter;B. Groessner-Schreiber;B. Noack;M. Nothnagel;N. E. Mokhtari;B. Loos;S. Jepsen;S. Schreiber
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作者：
A. Schaefer;G. Richter;B. Groessner-Schreiber;B. Noack;M. Nothnagel;N. E. Mokhtari;B. Loos;S. Jepsen;S. Schreiber
近年来的研究表明，冠心病和牙周炎之间存在着相互的流行病学关系。这两种疾病都与类似的危险因素有关，其特征是慢性炎症过程。在一项候选基因关联研究中，我们确定了两种疾病共有的遗传易感性位点的关联。我们证实了已知的人类染色体9p21.3上的两个相邻的连锁不平衡区域与CHD的关联，并显示了这些位点与侵袭性牙周炎风险的额外强关联。对于主要相关连锁不平衡区的前导SNP rs 1333048，常染色体隐性遗传模式的优势比对于全身性侵袭性牙周炎为1.99（95%置信区间1.33-2.94; P = 6.9610），对于局限性侵袭性牙周炎为1.72（1.06-2.76; P = 2.6610）。这两个相关的连锁不平衡区映射到大型反义非编码RNA ANRIL的序列，该序列部分重叠CDKN 2A/CDKN 2B的调控和编码序列。一个紧密定位的糖尿病相关的变异是独立的冠心病和牙周炎的风险单倍型。我们的研究表明，CHD和牙周炎至少有一个易感基因座，这可能是参与ANRIL的活动和独立的糖尿病相关的风险变量在该地区的遗传相关。阐明ANRIL转录变体的相互作用及其参与对交互性疾病CHD和牙周炎的易感性增加，有望对这些复杂常见疾病的潜在共同致病机制有新的认识。引文：Schaefer AS，Richter GM，Groessner-Schreiber B，Noack B，Nothnagel M等人（2009）冠心病和牙周炎共有遗传易感性位点的鉴定。PLoS Genet 5（2）：e1000378. doi：10.1371/journal.pgen.1000378编辑器：Jonathan Marchini，牛津大学，英国接收2008年9月3日;接受2009年1月12日;出版2009年2月13日版权：2009 Schaefer et al.这是一篇开放获取的文章，根据知识共享署名许可证的条款分发，该许可证允许在任何媒体上无限制地使用，分发和复制，但须注明原作者和来源。资金来源：本研究得到了克里斯蒂安-阿尔布雷希特大学医学系“炎症医学研究中心”研究基金的支持，该大学医学中心位于石勒苏益格-荷尔斯泰因，基尔校区（阿恩S。Schaefer & Gesa M. Richter），德国教育和研究部通过POPGEN生物库项目（01 GR 0468），由波恩大学医学系BONFOR（Søren Jepsen）和ARPA研究基金会（Birte Groessner-Schreiber & Søren Jepsen）（里根斯堡，德国）提供赠款。竞争利益：作者声明不存在竞争利益。* 电子邮件：a. ikmb.uni-kiel.de
Recent studies indicate a mutual epidemiological relationship between coronary heart disease (CHD) and periodontitis. Both diseases are associated with similar risk factors and are characterized by a chronic inflammatory process. In a candidategene association study, we identify an association of a genetic susceptibility locus shared by both diseases. We confirm the known association of two neighboring linkage disequilibrium regions on human chromosome 9p21.3 with CHD and show the additional strong association of these loci with the risk of aggressive periodontitis. For the lead SNP of the main associated linkage disequilibrium region, rs1333048, the odds ratio of the autosomal-recessive mode of inheritance is 1.99 (95% confidence interval 1.33–2.94; P = 6.9610) for generalized aggressive periodontitis, and 1.72 (1.06–2.76; P = 2.6610) for localized aggressive periodontitis. The two associated linkage disequilibrium regions map to the sequence of the large antisense noncoding RNA ANRIL, which partly overlaps regulatory and coding sequences of CDKN2A/ CDKN2B. A closely located diabetes-associated variant was independent of the CHD and periodontitis risk haplotypes. Our study demonstrates that CHD and periodontitis are genetically related by at least one susceptibility locus, which is possibly involved in ANRIL activity and independent of diabetes associated risk variants within this region. Elucidation of the interplay of ANRIL transcript variants and their involvement in increased susceptibility to the interactive diseases CHD and periodontitis promises new insight into the underlying shared pathogenic mechanisms of these complex common diseases. Citation: Schaefer AS, Richter GM, Groessner-Schreiber B, Noack B, Nothnagel M, et al. (2009) Identification of a Shared Genetic Susceptibility Locus for Coronary Heart Disease and Periodontitis. PLoS Genet 5(2): e1000378. doi:10.1371/journal.pgen.1000378 Editor: Jonathan Marchini, University of Oxford, United Kingdom Received September 3, 2008; Accepted January 12, 2009; Published February 13, 2009 Copyright: 2009 Schaefer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was supported by a research grant of the ‘‘Research Center Inflammation Medicine’’ of the Medical Faculty, Christian-Albrechts-University, University Medical Center Schleswig-Holstein, Campus Kiel, (Arne S. Schaefer & Gesa M. Richter), The German Ministry of Education and Research through the POPGEN biobank project (01GR0468), by a grant from BONFOR of the Medical Faculty, University of Bonn (Søren Jepsen) and a grant from the ARPA Research Foundation (Birte Groessner-Schreiber & Søren Jepsen), Regensburg, Germany. Competing Interests: The authors have declared that no competing interests exist. * E-mail: a.schaefer@ikmb.uni-kiel.de