DNMT3A 和 TET2；肥胖儿童和青少年通用 DNA 甲基化的潜在估计；与代谢失调的关系。
DNMT3A and TET2; Potential Estimates of Generic DNA Methylation in Children and Adolescents with Obesity; Relation to Metabolic Dysregulation.
机构信息
Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Department of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
出版信息
Horm Res Paediatr. 2022;95(1):25-34. doi: 10.1159/000521701. Epub 2022 Jan 21.
INTRODUCTION
The role of DNA methylation in metabolic dysregulation is emerging. However, the functional role of methylation in obesity and metabolic dysregulation is poorly understood.
AIM
The aim of this study was to compare DNA methyltransferase-3A (DNMT3A) and ten-eleven translocase-2 (TET2) levels in children and adolescents with obesity to normal-weighed children and adolescents and to correlate them to various metabolic parameters.
METHODS
Fifty children and adolescents with obesity were compared to 50 matched normal-weighed children and adolescents. Participants underwent assessment for anthropometric measurements, Tanner staging, acanthosis nigricans, and mean blood pressure percentile on three different occasions. TET2, DNMT3A, fasting lipids, and insulin were measured with calculation of the homeostatic model assessment insulin resistance (HOMA-IR).
RESULTS
The median BMI SDS of the studied children and adolescents with obesity was 3.40, their mean TET2 was 178.40 ng/mL, and their mean DNMT3A was 2.18 ng/mL. TET2 is significantly lower (p = 0.009), while DNMT3A is significantly higher (p < 0.001) in children and adolescents with obesity than controls. Children and adolescents with obesity and insulin resistance have significantly lower TET2 (p = 0.012) and significantly higher DNMT3A (p = 0.013) than those without insulin resistance. Diastolic blood pressure percentile and HOMA-IR are positively correlated to DNMT3A (p < 0.001) and negatively correlated to TET-2 (p < 0.001). Multivariate logistic regression analysis revealed that TET2 and DNMT3A are independently associated with diastolic blood pressure percentile (p = 0.03 and p = 0.014, respectively) and HOMA-IR (p = 0.003 and p = 0.001, respectively).
CONCLUSIONS
Children and adolescents with obesity have significantly higher DNMT3A and significantly lower TET2 than controls. This is more evident in those having insulin resistance than those without. DNMT3A and TET2 are independently associated with systemic hypertension and insulin resistance in children with obesity.
简介
DNA 甲基化在代谢失调中的作用正在显现。然而，甲基化在肥胖和代谢失调中的功能作用还知之甚少。
目的
本研究旨在比较肥胖儿童和青少年与正常体重儿童和青少年的 DNA 甲基转移酶 3A（DNMT3A）和 ten-eleven 转位酶 2（TET2）水平，并将其与各种代谢参数相关联。
方法
将 50 名肥胖儿童和青少年与 50 名匹配的正常体重儿童和青少年进行比较。参与者接受了三次不同的评估，包括人体测量学测量、Tanner 分期、黑棘皮病和平均血压百分位。使用稳态模型评估胰岛素抵抗（HOMA-IR）计算 TET2、DNMT3A、空腹血脂和胰岛素。
结果
研究中肥胖儿童和青少年的中位数 BMI SDS 为 3.40，平均 TET2 为 178.40ng/ml，平均 DNMT3A 为 2.18ng/ml。肥胖儿童和青少年的 TET2 显著降低（p=0.009），而 DNMT3A 显著升高（p<0.001）。有胰岛素抵抗的肥胖儿童和青少年的 TET2 显著降低（p=0.012），DNMT3A 显著升高（p=0.013）。舒张压百分位和 HOMA-IR 与 DNMT3A 呈正相关（p<0.001），与 TET-2 呈负相关（p<0.001）。多元逻辑回归分析显示，TET2 和 DNMT3A 与舒张压百分位（p=0.03 和 p=0.014）和 HOMA-IR（p=0.003 和 p=0.001）独立相关。
结论
肥胖儿童和青少年的 DNMT3A 显著升高，TET2 显著降低，与对照组相比。在有胰岛素抵抗的肥胖儿童和青少年中，这种情况更为明显。DNMT3A 和 TET2 与肥胖儿童的系统性高血压和胰岛素抵抗独立相关。
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