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2型糖尿病患者白细胞端粒长度缩短与LINE-1的DNA高甲基化有关。

The shortening of leukocyte telomere length relates to DNA hypermethylation of LINE-1 in type 2 diabetes mellitus.

作者信息

Wu Yue, Cui Wei, Zhang Donghong, Wu Wei, Yang Zhuo

机构信息

Department of Clinical Laboratory, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China.

出版信息

Oncotarget. 2017 May 22;8(43):73964-73973. doi: 10.18632/oncotarget.18167. eCollection 2017 Sep 26.

Abstract

BACKGROUND

We aim to investigate the cross-talking of leukocyte telomere length (LTL) and DNA methylation of LINE-1 in type 2 diabetes mellitus (T2DM).

RESULTS

LTL (ratio of the copy number of telomere [T] repeats to that of a single [S] gene) was significantly shortened in T2DM compared with controls (0.94 ± 0.41 vs. 1.14 ± 0.48, < 0.001), and decreased steadily with age in both controls and T2DM. Conversely, significant increase of LINE-1 DNA methylation was found in T2DM compared with controls (49.60 ± 14.55 vs. 37.81 ± 9.07, < 0.001). Moreover, age, HbA1c, and LINE-1 methylation ratio were stably negatively related with LTL after multi-adjustment. Shorter LTL was associated with an increased risk of T2DM [adjusted OR (95% CI) = 2.458 (1.192, 5.070), 0.015], while lower LINE-1 DNA methylation levels could reduce the risk of T2DM [adjusted OR (95% CI) = 0.189 (0.089, 0.400), < 0.001].

MATERIALS AND METHODS

We performed a hospital-based case-control study of 205 T2DM patients and 213 subjects of healthy control with sex and age matched. LTL and DNA methylation of LINE-1 was measured by quantitative PCR and quantitative methylation-specific PCR (qMSP), respectively.

CONCLUSIONS

Our research demonstrates the association between shorter LTL and LINE-1 hyper-methylation in Chinese T2DM patients. These findings suggest that shorter LTL might be associated with T2DM in a manner dependent of epigenetic level.

摘要

背景

我们旨在研究2型糖尿病(T2DM)中白细胞端粒长度(LTL)与LINE-1 DNA甲基化之间的相互作用。

结果

与对照组相比,T2DM患者的LTL(端粒重复序列拷贝数与单个[S]基因拷贝数之比)显著缩短(0.94±0.41 vs. 1.14±0.48,<0.001),且在对照组和T2DM患者中均随年龄稳步下降。相反,与对照组相比,T2DM患者中LINE-1 DNA甲基化显著增加(49.60±14.55 vs. 37.81±9.07,<0.001)。此外,在多因素调整后,年龄、糖化血红蛋白(HbA1c)和LINE-1甲基化率与LTL呈稳定的负相关。较短的LTL与T2DM风险增加相关[调整后比值比(95%置信区间)=2.458(1.192,5.070),P=0.015],而较低的LINE-1 DNA甲基化水平可降低T2DM风险[调整后比值比(95%置信区间)=0.189(0.089,0.400),<0.001]。

材料与方法

我们进行了一项基于医院的病例对照研究,纳入205例T2DM患者和213例年龄和性别匹配的健康对照者。分别采用定量PCR和定量甲基化特异性PCR(qMSP)检测LTL和LINE-1的DNA甲基化。

结论

我们的研究证实了中国T2DM患者中较短的LTL与LINE-1高甲基化之间的关联。这些发现表明,较短的LTL可能通过表观遗传水平与T2DM相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85ed/5650315/f3518decb27c/oncotarget-08-73964-g001.jpg

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