Baker Heart and Diabetes Institute, Epigenetics in Human Health and Disease Program, Melbourne, Vic, Australia; Department of Diabetes, Central Clinical School, Monash University, Melbourne, Vic, Australia.
Wardliparingga Aboriginal Health Equity Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia; Faculty of Health and Medical Sciences, University of Adelaide, South Australia, Australia.
Diabetes Res Clin Pract. 2023 Oct;204:110918. doi: 10.1016/j.diabres.2023.110918. Epub 2023 Sep 24.
To investigate epigenomic indices of diabetic kidney disease (DKD) susceptibility among high-risk populations with type 2 diabetes mellitus.
KDIGO (Kidney Disease: Improving Global Outcomes) clinical guidelines were used to classify people living with or without DKD. Differential gene methylation of DKD was then assessed in a discovery Aboriginal Diabetes Study cohort (PROPHECY, 89 people) and an external independent study from Thailand (THEPTARIN, 128 people). Corresponding mRNA levels were also measured and linked to levels of albuminuria and eGFR.
Increased DKD risk was associated with reduced methylation and elevated gene expression in the PROPHECY discovery cohort of Aboriginal Australians and these findings were externally validated in the THEPTARIN diabetes registry of Thai people living with type 2 diabetes mellitus.
Novel epigenomic scores can improve diagnostic performance over clinical modelling using albuminuria and GFR alone and can distinguish DKD susceptibility.
在患有 2 型糖尿病的高危人群中，研究糖尿病肾病 (DKD) 易感性的表观基因组学指标。
KDIGO（肾脏疾病：改善全球预后）临床指南用于对患有或不患有 DKD 的人群进行分类。然后，在一个发现性的澳大利亚原住民糖尿病研究队列（PROPHECY，89 人）和一个来自泰国的独立外部研究（THEPTARIN，128 人）中评估 DKD 的差异基因甲基化。还测量了相应的 mRNA 水平，并将其与白蛋白尿和 eGFR 水平相关联。
在澳大利亚原住民的 PROPHECY 发现队列中，DKD 风险增加与甲基化减少和基因表达升高有关，这些发现在外源性泰国 2 型糖尿病患者的 THEPTARIN 糖尿病登记处得到了验证。
新型表观基因组评分可以提高基于白蛋白尿和 GFR 的临床模型的诊断性能，并可以区分 DKD 的易感性。
