Duggan Catherine, Xiao Liren, Terry Mary Beth, McTiernan Anne
Epidemiology Program, Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
Obesity (Silver Spring). 2014 Sep;22(9):2091-6. doi: 10.1002/oby.20806. Epub 2014 Jun 13.
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.
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.
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.
Our results suggest that lifestyle changes sufficient to significantly reduce weight over 12-months may not change LINE-1 DNA methylation levels.
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。
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。
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。
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。