Differentially Methylated DNA Regions and Left Ventricular Hypertrophy in African Americans: A HyperGEN Study.
Differentially Methylated DNA Regions and Left Ventricular Hypertrophy in African Americans: A HyperGEN Study.
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作者：
左心室肥厚 (LVH) 是心血管疾病的独立危险因素，非裔美国人患 LVH 的风险不同。遗传学研究已经确定了与该病症相关的潜在候选基因和变异。表观遗传修饰可能继续帮助揭示疾病机制。我们使用从高血压遗传流行病学网络 (HyperGEN) 中选出的 636 名非裔美国人的甲基化和超声心动图数据来识别与 LVH 相关的差异甲基化区域 (DMR)。从全血中提取的 DNA 在 Illumina Mmethyl450 阵列上进行分析。我们拟合线性混合模型来检查共甲基化区域和 LV 性状之间的关联，然后我们在显着的 DMR 内进行单一 CpG 分析。我们确定了 DMR 与射血分数 (XKR6)、左室舒张内径 (TRAK1)、左室质量指数 (GSE1、RPS15 A、PSMD7) 和相对壁厚度 (DNHD1) 之间的关联。在单个 CpG 分析中，注释为 TRAK1 和 DNHD1 的 CpG 位点非常重要。这些 CpG 与复制队列中的 LV 特征无关，但 DNHD1 的作用方向在各队列中是一致的。值得注意的是，DNHD1、GSE1 和 PSMD7 可能有助于心脏结构功能。未来的研究应该评估区域 DNA 甲基化模式与 LVH 发展之间的关系。
Left ventricular (LV) hypertrophy (LVH) is an independent risk factor for cardiovascular disease, and African Americans experience a disparate high risk of LVH. Genetic studies have identified potential candidate genes and variants related to the condition. Epigenetic modifications may continue to help unravel disease mechanisms. We used methylation and echocardiography data from 636 African Americans selected from the Hypertension Genetic Epidemiology Network (HyperGEN) to identify differentially methylated regions (DMRs) associated with LVH. DNA extracted from whole blood was assayed on Illumina Methyl450 arrays. We fit linear mixed models to examine associations between co-methylated regions and LV traits, and we then conducted single CpG analyses within significant DMRs. We identified associations between DMRs and ejection fraction (XKR6), LV internal diastolic dimension (TRAK1), LV mass index (GSE1, RPS15 A, PSMD7), and relative wall thickness (DNHD1). In single CpG analysis, CpG sites annotated to TRAK1 and DNHD1 were significant. These CpGs were not associated with LV traits in replication cohorts but the direction of effect for DNHD1 was consistent across cohorts. Of note, DNHD1, GSE1, and PSMD7 may contribute to cardiac structural function. Future studies should evaluate relationships between regional DNA methylation patterns and the development of LVH.
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影响因子：
8.3
作者：
Drazner, MH;Dries, DL;Victor, RG
通讯作者：
Victor, RG
影响因子：
4.9
作者：
de Simone, Giovanni;Tang, Weihong;Arnett, Donna K.
通讯作者：
Arnett, Donna K.
DOI：
10.1161/hhf.0b013e318291329a
发表时间：
2013-05
期刊：
Circulation. Heart failure
影响因子：
--
作者：
Heidenreich PA;Albert NM;Allen LA;Bluemke DA;Butler J;Fonarow GC;Ikonomidis JS;Khavjou O;Konstam MA;Maddox TM;Nichol G;Pham M;Piña IL;Trogdon JG;American Heart Association Advocacy Coordinating Committee;Council on Arteriosclerosis, Thrombosis and Vascular Biology;Council on Cardiovascular Radiology and Intervention;Council on Clinical Cardiology;Council on Epidemiology and Prevention;Stroke Council
通讯作者：
Stroke Council
影响因子：
2.1
作者：
Kianu Phanzu B;Nkodila Natuhoyila A;Kintoki Vita E;M'Buyamba Kabangu JR;Longo-Mbenza B
通讯作者：
Longo-Mbenza B
影响因子：
--
作者：
Jin, Yu;Kuznetsova, Tatiana;Staessen, Jan A.
通讯作者：
Staessen, Jan A.