Clinical Research Papers:

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

Shasha Meng, Shaowei Wu, Liming Liang, Geyu Liang, Edward Giovannucci, Immaculata De Vivo _ and Hongmei Nan

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Oncotarget. 2016; 7:60676-60686. https://doi.org/10.18632/oncotarget.10325

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Shasha Meng1, Shaowei Wu2, Liming Liang1, Geyu Liang4, Edward Giovannucci1,3,5, Immaculata De Vivo1,3,*, Hongmei Nan6,7,*

1Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA

2Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA

3Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

4Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu, China

5Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA

6Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA

7Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA

*Co-senior authors

Correspondence to:

Immaculata De Vivo, email: [email protected]

Hongmei Nan, email: [email protected]

Keywords: mitochondrial DNA copy number, anthropometric indices, weight change, telemere length

Received: May 09, 2016    Accepted: June 09, 2016    Published: June 29, 2016


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.

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