Charité - University Medicine Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute for Dental and Craniofacial Sciences, Department of Periodontology and Synoptic Dentistry, Berlin, Germany.
Institute for Cardiogenetics, University of Lübeck, 23562, Lübeck, Germany.
Sci Rep. 2018 Sep 12;8(1):13678. doi: 10.1038/s41598-018-31980-8.
Evidence for a shared genetic basis of association between coronary artery disease (CAD) and periodontitis (PD) exists. To explore the joint genetic basis, we performed a GWAS meta-analysis. In the discovery stage, we used a German aggressive periodontitis sample (AgP-Ger; 680 cases vs 3,973 controls) and the CARDIoGRAMplusC4D CAD meta-analysis dataset (60,801 cases vs 123,504 controls). Two SNPs at the known CAD risk loci ADAMTS7 (rs11634042) and VAMP8 (rs1561198) passed the pre-assigned selection criteria (P < 0.05; P < 5 × 10; concordant effect direction) and were replicated in an independent GWAS meta-analysis dataset of PD (4,415 cases vs 5,935 controls). SNP rs1561198 showed significant association (PD[Replication]: P = 0.008 OR = 1.09, 95% CI = [1.02-1.16]; PD [Discovery + Replication]: P = 0.0002, OR = 1.11, 95% CI = [1.05-1.17]). For the associated haplotype block, allele specific cis-effects on VAMP8 expression were reported. Our data adds to the shared genetic basis of CAD and PD and indicate that the observed association of the two disease conditions cannot be solely explained by shared environmental risk factors. We conclude that the molecular pathway shared by CAD and PD involves VAMP8 function, which has a role in membrane vesicular trafficking, and is manipulated by pathogens to corrupt host immune defense.
存在冠状动脉疾病（CAD）和牙周炎（PD）之间关联的共同遗传基础的证据。为了探索联合遗传基础，我们进行了 GWAS 荟萃分析。在发现阶段，我们使用了德国侵袭性牙周炎样本（AgP-Ger；680 例 vs 3973 例对照）和 CARDIoGRAMplusC4D CAD 荟萃分析数据集（60801 例 vs 123504 例对照）。两个位于已知 CAD 风险位点 ADAMTS7（rs11634042）和 VAMP8（rs1561198）的 SNP 通过了预先指定的选择标准（P < 0.05；P < 5×10；一致的效应方向），并在 PD 的独立 GWAS 荟萃分析数据集中得到了复制（4415 例 vs 5935 例对照）。SNP rs1561198 显示出显著的相关性（PD[复制]：P = 0.008 OR = 1.09，95%CI = [1.02-1.16]；PD [发现+复制]：P = 0.0002，OR = 1.11，95%CI = [1.05-1.17]）。对于相关的单倍型块，报告了 VAMP8 表达的等位基因特异性顺式效应。我们的数据增加了 CAD 和 PD 的共同遗传基础，并表明两种疾病状况的观察到的关联不能仅仅用共同的环境危险因素来解释。我们得出结论，CAD 和 PD 之间共享的分子途径涉及 VAMP8 功能，它在膜小泡运输中起作用，并被病原体操纵以破坏宿主免疫防御。
