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绝经后超重女性外周血白细胞中,体重减轻对LINE-1甲基化水平无影响。

No effect of weight loss on LINE-1 methylation levels in peripheral blood leukocytes from postmenopausal overweight women.

作者信息

Duggan Catherine, Xiao Liren, Terry Mary Beth, McTiernan Anne

机构信息

Epidemiology Program, Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.

出版信息

Obesity (Silver Spring). 2014 Sep;22(9):2091-6. doi: 10.1002/oby.20806. Epub 2014 Jun 13.

Abstract

OBJECTIVES

Obesity and weight-loss are associated with methylation patterns in specific genes, but their effect on Long Interspersed Nuclear Elements (LINE-1) methylation, a measure of global methylation is largely unknown.

METHODS

Three hundred overweight/obese post-menopausal women (50-75 years) were part of a completed, 1-year randomized controlled trial, comparing independent and combined effects of a reduced-calorie weight-loss diet, and exercise program, versus control. DNA was extracted from peripheral blood leukocytes collected at baseline and 12-months, and LINE-1 methylation analyzed by pyrosequencing. Mean changes between groups using generalized estimating equations and examined effects of weight-loss on LINE-1 methylation using stratified analyses (gained weight/no weight-loss [N = 84]; <5% [N = 45]; 5%-10% [N = 45]; >10% of baseline weight-loss [N = 126]) within each arm, adjusted by blood cell counts were compared. Associations between LINE-1 methylation and previously measured biomarkers, and anthropometrics were also examined.

RESULTS

No significant difference in LINE-1 methylation levels was detected in any intervention group versus controls. The magnitude of weight-loss was not associated with LINE-1 methylation at 12-months. There were no associations between baseline characteristics of participants, or previously measured biomarkers, and LINE-1 methylation.

CONCLUSIONS

Our results suggest that lifestyle changes sufficient to significantly reduce weight over 12-months may not change LINE-1 DNA methylation levels.

摘要

目的

肥胖和体重减轻与特定基因的甲基化模式相关,但它们对长散在核元件(LINE-1)甲基化(一种整体甲基化的测量指标)的影响在很大程度上尚不清楚。

方法

三百名超重/肥胖的绝经后女性(50 - 75岁)参与了一项为期1年的完整随机对照试验,比较了低热量减肥饮食和运动计划单独及联合作用与对照组的效果。从基线和12个月时采集的外周血白细胞中提取DNA,并通过焦磷酸测序分析LINE-1甲基化。使用广义估计方程比较组间的平均变化,并通过分层分析(体重增加/未减重[N = 84];体重减轻<5%[N = 45];体重减轻5% - 10%[N = 45];体重减轻>基线体重的10%[N = 126])研究体重减轻对各臂内LINE-1甲基化的影响,经血细胞计数调整后进行比较。还研究了LINE-1甲基化与先前测量的生物标志物和人体测量学指标之间的关联。

结果

在任何干预组与对照组之间均未检测到LINE-1甲基化水平的显著差异。12个月时体重减轻的幅度与LINE-1甲基化无关。参与者的基线特征或先前测量的生物标志物与LINE-1甲基化之间均无关联。

结论

我们的结果表明,在12个月内足以显著减轻体重的生活方式改变可能不会改变LINE-1 DNA甲基化水平。

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