Evaluating the role of epigenetic histone modifications in the metabolic memory of type 1 diabetes.
Evaluating the role of epigenetic histone modifications in the metabolic memory of type 1 diabetes.
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DOI：
10.2337/db13-1251
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发表时间：
2014-05
期刊：
影响因子：
7.7
通讯作者：
DCCT/EDIC Research Group
中科院分区：
文献类型：
--
作者：
Miao F;Chen Z;Genuth S;Paterson A;Zhang L;Wu X;Li SM;Cleary P;Riggs A;Harlan DM;Lorenzi G;Kolterman O;Sun W;Lachin JM;Natarajan R;DCCT/EDIC Research Group
在糖尿病干预和并发症的长期流行病学（EDIC）研究中，我们评估了在糖尿病控制和并发症试验（DCCT）中，表观遗传组蛋白翻译后修饰是否与强化治疗与常规治疗的长期有益效果（代谢记忆）有关。我们对30名DCCT常规治疗组（病例组：DCCT平均HbA1c水平>9.1% [76 mmol/mol]，以及EDIC随访第10年视网膜病变或肾病的进展）和30名DCCT强化治疗组(对照组：平均DCCT HbA1c水平<7.3% [56 mmol/mol]，无视网膜病变或肾病进展)。与对照组相比，病例组单核细胞中H3K9Ac（活性染色质标记）富集的启动子区域数量有统计学意义（P = 0.0096）。在两组合并的患者中，单核细胞H3K9Ac与DCCT和EDIC期间的平均HbA1c水平显著相关（P < 2.2E-16）。值得注意的是，前38例高乙酰化启动子（P < 0.05）包含与核因子-κB炎症通路相关的bbb15基因，并且富含与糖尿病并发症相关的基因。这些结果表明HbA1c水平与H3K9Ac之间存在关联，并且可能是人类代谢记忆的表观遗传学解释。
We assessed whether epigenetic histone posttranslational modifications are associated with the prolonged beneficial effects (metabolic memory) of intensive versus conventional therapy during the Diabetes Control and Complications Trial (DCCT) on the progression of microvascular outcomes in the long-term Epidemiology of Diabetes Interventions and Complications (EDIC) study. We performed chromatin immunoprecipitation linked to promoter tiling arrays to profile H3 lysine-9 acetylation (H3K9Ac), H3 lysine-4 trimethylation (H3K4Me3), and H3K9Me2 in blood monocytes and lymphocytes obtained from 30 DCCT conventional treatment group subjects (case subjects: mean DCCT HbA1c level >9.1% [76 mmol/mol] and progression of retinopathy or nephropathy by EDIC year 10 of follow-up) versus 30 DCCT intensive treatment subjects (control subjects: mean DCCT HbA1c level <7.3% [56 mmol/mol] and without progression of retinopathy or nephropathy). Monocytes from case subjects had statistically greater numbers of promoter regions with enrichment in H3K9Ac (active chromatin mark) compared with control subjects (P = 0.0096). Among the patients in the two groups combined, monocyte H3K9Ac was significantly associated with the mean HbA1c level during the DCCT and EDIC (each P < 2.2E-16). Of note, the top 38 case hyperacetylated promoters (P < 0.05) included >15 genes related to the nuclear factor-κB inflammatory pathway and were enriched in genes related to diabetes complications. These results suggest an association between HbA1c level and H3K9Ac, and a possible epigenetic explanation for metabolic memory in humans.
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影响因子：
7.7
作者：
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