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首页> 外文期刊>BMC Medical Genomics >Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus
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Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus

机译：全基因组DNA甲基化分析用于1型糖尿病的糖尿病肾病

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Background 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. Methods 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. Results 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. Conclusion 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.
机译：背景技术糖尿病性肾病是糖尿病的严重并发症，并且与相当大的发病率和高死亡率有关。越来越多的证据表明表观基因组的失调与糖尿病性肾病有关。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，我们评估了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T1D和肾病，而对照组患有T1D，但没有肾脏疾病的证据。方法使用最新开发的Illumina Infinium ？ HumanMethylation27 BeadChip在病例和对照中的亚硫酸氢盐转化的DNA中进行DNA甲基化谱分析，从而可以直接研究整个基因组中CpG位点的27,578个胞嘧啶，这是重点在14,495个基因的启动子区域。结果奇异值分解（SVD）分析表明，DNA甲基化变异的重要组成部分与患者的年龄，糖尿病性肾病的发作时间以及性别有关。使用多元Cox回归分析调整混杂因素，并以0.05的错误发现率（FDR）观察到19个CpG位点，这些位点与糖尿病性肾病的发展时间相关。值得注意的是，这包括一个位于UNC13B转录起始位点上游18 bp的CpG位点，该基因最近报道了第一个内含子SNP rs13293564与糖尿病性肾病有关。结论该高通量平台能够成功询问单个胞嘧啶的甲基化状态，并鉴定出19个与糖尿病肾病风险相关的前瞻性CpG位点。 DNA甲基化的这些差异值得在复制研究中进行进一步的随访，该研究使用了更大的患有和不患有肾病的糖尿病患者。

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