Leukocyte mitochondrial DNA copy number, anthropometric indices, and weight change in US women

Leukocyte mitochondrial DNA copy number, anthropometric indices, and weight change in US women
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DOI:
10.18632/oncotarget.10325
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发表时间:
2016-09-13
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影响因子:
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通讯作者:
Nan, Hongmei
Nan, Hongmei
中科院分区:
其他
文献类型:
--
作者:
Meng, Shasha;Wu, Shaowei;Nan, Hongmei

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目的:研究白细胞线粒体DNA拷贝数(MTCN)与不同人体测量学指标和体重变化的关系,比较MTCN和端粒长度与BMI和年龄的关系。设计:基于人群的队列研究。地点:护士健康研究,对1976年登记的121,700名护士进行前瞻性队列研究;在1989-1990年间,一组32,826名妇女提供了血液样本。参与者:1700名来自护士健康研究的病例对照研究中嵌套的MTCN和端粒长度,她们也进行了人体测量。主要观察指标:用实时定量聚合酶链式反应和初始问卷的各种人体测量数据测量外周血白细胞相对MTCN和端粒长度。结果:白细胞MTCN与当前体重呈负相关(LS平均值:Q1-Q4:0.07,0.04,0.03,-0.17;P-趋势=0.002.11,-0.0 1,-0.0 4,-0.2 5;腰臀比(LS=Q1-Q4:0.0001.0 6、0.0 8、-0.0 4、-0.0 6;P趋势=0.0 3)。MTCN z得分降低一个单位,相当于一个5英尺10英寸的成年人体重增加了大约3.5磅。此外,体重增加与MTCN呈双向负相关。此外,MTcn与端粒长度呈显著正相关(LS均值Q1-Q4:-0.02,0.09,0.11,0.33;P-Trend<0.0001)。调整端粒长度后,MTcn与体重指数呈负相关(P(趋势)=0.003),而端粒长度与体重指数无关。另一方面,调整MTCN后,端粒长度与年龄呈负相关(P-趋势=0.04),而MTCN与年龄无关。结论:我们的结果为线粒体介导的氧化应激防御机制与体重变化之间潜在的双向时间关系提供了令人信服的证据。
Objectives: To examine the association between leukocyte mitochondrial DNA copy number (mtCN) and different anthropometric indices as well as weight changes; and to compare mtCN and telomere length with respect to their associations with BMI and age.Design: Population based cohort study.Setting: Nurses' Health Study, an ongoing prospective cohort study of 121,700 nurses enrolled in 1976; in 1989-1990 a subset of 32,826 women provided blood samples.Participants: 1,700 disease-free US women from case-control studies nested within the Nurses' Health Study with mtCN and telomere length measured who also have anthropometric measurements.Main outcome measure: Relative mtCN and telomere lengths in peripheral blood leukocytes measured by quantitative real time polymerase chain reaction and various anthropometric measurements data from initial questionnaire.Results: Leukocyte mtCN was inversely associated with current weight (LS means Q1-Q4: 0.07, 0.04, 0.03, -0.17; P-trend = 0.002), waist size (LS means Q1-Q4: 0.06, 0.05, -0.04, -0.06; P-trend = 0.04), BMI (LS means normal light, normal heavy, overweight, pre-obese, obese: 0.11, -0.01, -0.04, 0.04, -0.25; P-trend < 0.0001), and waist-hip ratio (WHR) (LS means Q1-Q4: 0.06, 0.08, -0.04, -0.06; P-trend = 0.03). A one-unit decrease in mtCN z score was equivalent to approximately 3.5 pounds of weight gain for an adult of 5'10 ''. In addition, weight gain was bi-directionally and inversely associated with mtCN. Moreover, mtCN was strongly positively correlated with telomere length (LS means Q1-Q4: -0.02, 0.09, 0.11, 0.33; P-trend < 0.0001). MtCN was inversely associated with BMI even after adjusting for telomere length (P (trend) = 0.003), while telomere length was not associated with BMI. On the other hand, telomere length was inversely associated with age after adjusting for mtCN (P-trend = 0.04), while mtCN was not associated with age.Conclusions: Our results provide compelling evidence for a potential bi-directional temporal relationship between mitochondrial-mediated oxidative stress-defense mechanisms and weight change.