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

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

Yue Wu  1   2 , Wei Cui  1   2 , Donghong Zhang  3   4 , Wei Wu  2 , Zhuo Yang  2
Affiliations

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

Yue Wu et al. Oncotarget. .

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.

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

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Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no competing financial interests.

Figures

Figure 1
Figure 1
Linear regression analysis of the association between leukocyte telomere length (LTL) (A) and LINE-1 methylation ratio (B) with age in controls and T2DM patients; Controls are shown as blue dots (n = 213), and T2DM patients as purple triangles (n = 205). As well as correlation of LTL with ln-FBG (C) and ln-HbA1c (D), and LINE-1 methylation ratio with ln-FBG (E) and ln-HbA1c (F). LTL is plotted as T/S ratio (ratio of the copy number of telomere (T) repeats to that of a single (S) gene). FBG and HbA1c values were ln-transformed and described as ln-FBG and ln-HbA1c to normalize the distributions with no skew.
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