Oncotarget

Research Papers:

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

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

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Oncotarget. 2017; 8:73964-73973. https://doi.org/10.18632/oncotarget.18167

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Abstract

Yue Wu1,2, Wei Cui1,2, Donghong Zhang3,4, Wei Wu2 and Zhuo Yang2

1Department of Clinical Laboratory, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

2Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China

3Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China

4Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA

Correspondence to:

Wei Cui, email: [email protected]

Donghong Zhang, email: [email protected]

Keywords: type 2 diabetes mellitus, leukocyte telomere length, DNA methylation, LINE-1, glycated hemoglobin

Received: April 04, 2017     Accepted: May 11, 2017     Published: May 22, 2017

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, P < 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, P < 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), P = 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), P < 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.


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