Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus.
Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus.
复制标题
DOI：
10.1186/1755-8794-3-33
复制
发表时间：
2010-08-05
影响因子：
2.7
通讯作者：
Savage DA
中科院分区：
文献类型：
--
作者：
Bell CG;Teschendorff AE;Rakyan VK;Maxwell AP;Beck S;Savage DA
糖尿病肾病是糖尿病的严重并发症，具有相当高的发病率和高死亡率。越来越多的证据表明表观基因组失调与糖尿病肾病有关。我们在一项针对 192 名爱尔兰 1 型糖尿病 (T1D) 患者的病例对照研究中评估了 DNA 甲基化的表观遗传修饰是否与糖尿病肾病相关。病例患有 1 型糖尿病和肾病，而对照组患有 1 型糖尿病，但没有肾脏疾病的证据。我们使用最近开发的 Illumina Infinium® HumanMmethylation27 BeadChip 对来自病例和对照的亚硫酸氢盐转化的 DNA 进行了 DNA 甲基化分析，该芯片能够直接研究整个基因组中 CpG 位点的 27,578 个单个胞嘧啶，这些胞嘧啶主要集中在 14,495 个基因的启动子区域。奇异值分解（SVD）分析表明，DNA 甲基化变异的重要组成部分与患者年龄、糖尿病肾病发病时间和性别相关。使用多变量 Cox 回归分析调整混杂因素，并在错误发现率 (FDR) 为 0.05 的情况下，我们观察到 19 个 CpG 位点，这些位点显示出与糖尿病肾病发展时间的相关性。值得注意的是，其中包括位于 UNC13B 转录起始位点上游 18 bp 的一个 CpG 位点，最近报道该基因的第一个内含子 SNP rs13293564 与糖尿病肾病相关。这个高通量平台能够成功询问单个胞嘧啶的甲基化状态，并确定了 19 个与糖尿病肾病风险相关的潜在 CpG 位点。 DNA 甲基化的这些差异值得在更大的患有或不患有肾病的糖尿病患者队列中进行复制研究中进一步随访。
Diabetic nephropathy is a serious complication of diabetes mellitus and is associated with considerable morbidity and high mortality. There is increasing evidence to suggest that dysregulation of the epigenome is involved in diabetic nephropathy. We assessed whether epigenetic modification of DNA methylation is associated with diabetic nephropathy in a case-control study of 192 Irish patients with type 1 diabetes mellitus (T1D). Cases had T1D and nephropathy whereas controls had T1D but no evidence of renal disease. We performed DNA methylation profiling in bisulphite converted DNA from cases and controls using the recently developed Illumina Infinium® HumanMethylation27 BeadChip, that enables the direct investigation of 27,578 individual cytosines at CpG loci throughout the genome, which are focused on the promoter regions of 14,495 genes. Singular Value Decomposition (SVD) analysis indicated that significant components of DNA methylation variation correlated with patient age, time to onset of diabetic nephropathy, and sex. Adjusting for confounding factors using multivariate Cox-regression analyses, and with a false discovery rate (FDR) of 0.05, we observed 19 CpG sites that demonstrated correlations with time to development of diabetic nephropathy. Of note, this included one CpG site located 18 bp upstream of the transcription start site of UNC13B, a gene in which the first intronic SNP rs13293564 has recently been reported to be associated with diabetic nephropathy. This high throughput platform was able to successfully interrogate the methylation state of individual cytosines and identified 19 prospective CpG sites associated with risk of diabetic nephropathy. These differences in DNA methylation are worthy of further follow-up in replication studies using larger cohorts of diabetic patients with and without nephropathy.
登录
查看更多内容
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
5.5
作者：
Goldenberg, Neil M.;Silverman, Mel
通讯作者：
Silverman, Mel
影响因子：
4.5
作者：
Krause, Bernardo;Sobrevia, Luis;Casanello, Paola
通讯作者：
Casanello, Paola
通过替代变量分析捕获基因表达研究中的异质性。
影响因子：
4.5
作者：
Leek, Jeffrey T.;Storey, John D.
通讯作者：
Storey, John D.
影响因子：
1.9
作者：
Leak TS;Perlegas PS;Smith SG;Keene KL;Hicks PJ;Langefeld CD;Mychaleckyj JC;Rich SS;Kirk JK;Freedman BI;Bowden DW;Sale MM
通讯作者：
Sale MM