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与 2 型糖尿病相比,HNF1A 变异诱导的糖尿病患者循环 miR-122 水平较低。

Lower Circulating miR-122 Level in Patients with HNF1A Variant-Induced Diabetes Compared with Type 2 Diabetes.

机构信息

Department of Endocrinology and Metabolism, Peking University People's Hospital, Peking University Diabetes Center, Beijing, 100044, China.

出版信息

J Diabetes Res. 2018 Aug 1;2018:7842064. doi: 10.1155/2018/7842064. eCollection 2018.

DOI:10.1155/2018/7842064
PMID:30155490
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6093029/
Abstract

miR-122, the expression of which is regulated by several transcription factors, such as HNF1A, was recently reported to be associated with type 2 diabetes (T2DM) and hepatocellular carcinoma. HNF1A variants can cause diabetes and might be involved in the development of primary liver neoplasm. Differences in miR-122 expression among different types of diabetes have not been studied. This study aimed to investigate differences in serum miR-122 levels in Chinese patients with different forms of diabetes, including T2DM, type 1 diabetes (T1DM), HNF1A variant-induced diabetes (HNF1A-DM), glucokinase variant-induced diabetes (GCK-DM), and mitochondrial A3243G mutation-induced diabetes (MDM). In total, 12 HNF1A-DM patients, 24 gender-, age-, and body mass index-matched (1 : 2) T2DM patients and 24 healthy subjects were included in this study. In addition, 30 monogenic diabetes (11 GCK-DM and 19 MDM) and 17 T1DM patients were included. Fasted blood biochemistry and miR-122 were measured. The results showed that the HNF1A-DM patients had lower miR-122 levels [0.046 (0.023, 0.121)] than T2DM patients [0.165 (0.036, 0.939), = 0.02] and healthy controls [0.249 (0.049, 1.234), = 0.019]. The area under the curve of the receiver operating characteristic curve for miR-122 to discriminate HNF1A-DM and T2DM was 0.687 (95% CI: 0.52-0.86, = 0.07). There was no difference in serum miR-122 among HNF1A-DM, GCK-DM, MDM, and T1DM patients. Lower serum miR-122 is a unique feature of HNF1A-DM patients and might partially explain the increased risk for liver neoplasm and abnormal lipid metabolism in HNF1A-DM patients.

摘要

miR-122 的表达受多种转录因子的调控,如 HNF1A,最近有报道称其与 2 型糖尿病(T2DM)和肝细胞癌有关。HNF1A 变异可导致糖尿病,并且可能与原发性肝肿瘤的发生有关。不同类型糖尿病患者血清 miR-122 表达的差异尚未得到研究。本研究旨在探讨中国不同类型糖尿病患者血清 miR-122 水平的差异,包括 T2DM、1 型糖尿病(T1DM)、HNF1A 变异诱导的糖尿病(HNF1A-DM)、葡萄糖激酶变异诱导的糖尿病(GCK-DM)和线粒体 A3243G 突变诱导的糖尿病(MDM)。本研究共纳入 12 例 HNF1A-DM 患者、24 例性别、年龄和体重指数匹配(1:2)的 T2DM 患者和 24 例健康对照者。此外,还纳入了 30 例单基因糖尿病(11 例 GCK-DM 和 19 例 MDM)和 17 例 T1DM 患者。检测空腹血生化和 miR-122。结果显示,HNF1A-DM 患者的 miR-122 水平[0.046(0.023,0.121)]低于 T2DM 患者[0.165(0.036,0.939), = 0.02]和健康对照组[0.249(0.049,1.234), = 0.019]。miR-122 区分 HNF1A-DM 和 T2DM 的受试者工作特征曲线下面积为 0.687(95%CI:0.52-0.86, = 0.07)。HNF1A-DM、GCK-DM、MDM 和 T1DM 患者血清 miR-122 水平无差异。血清 miR-122 水平降低是 HNF1A-DM 患者的一个独特特征,可能部分解释了 HNF1A-DM 患者肝肿瘤风险增加和脂质代谢异常的原因。

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