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Mitochondrial genetic haplogroups and incident obesity: a longitudinal cohort study

European Journal of Clinical Nutrition volume 72, pages 587–592 (2018)Cite this article

Subjects

Abstract

Background/Objectives

A small number of case–control studies have suggested that mitochondrial haplogroups could be associated with obesity. We examined whether obesity risk was influenced by mitochondrial haplogroup in a large North American cohort across an 8-year period. We conducted a longitudinal cohort study including individuals from the Osteoarthritis Initiative.

Subjects/Methods

Mitochondrial haplogroups were determined by sequencing and PCR-RFLP techniques using this nomenclature: HV, JT, KU, IWX, and super HV/others. The strength of the association between mitochondrial haplogroups and incident obesity was quantified with hazard ratios (HRs), adjusted for potential confounders using a Cox’s regression analysis.

Results

Overall, 2342 non-obese Caucasian participants (56.7% women) with a mean ± SD age of 62.0 ± 9.5 years at baseline were included. During a median follow-up of 8 years, 334 individuals ( = 14.3% of baseline population) became obese. After adjusting for nine potential confounders, the haplogroups IWX carried a significant 48% higher risk of obesity (HR = 1.48; 95% CI: 1.02–2.39) compared to the HV haplotype (the most frequent type).

Conclusion

Only the presence of the IWX haplogroups appears to be linked to increased obesity risk, independent of potential baseline confounders. Future cohort studies are needed to confirm these findings and to determine potential underlying mechanisms.

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References

  1. Wang Y, Brinton RD. Triad of risk for late onset Alzheimer’s: mitochondrial haplotype, APOE genotype and chromosomal sex. Front Aging Neurosci. 2016;8:232.

    PubMed  PubMed Central  Google Scholar 

  2. Copeland WC, Longley MJ. Mitochondrial genome maintenance in health and disease. DNA Repair (Amst). 2014;19:190–8.

    Article  CAS  Google Scholar 

  3. Wallace DC, Chalkia D. Mitochondrial DNA genetics and the heteroplasmy conundrum in evolution and disease. Cold Spring Harb Perspect Biol. 2013;5:a021220.

    Article  Google Scholar 

  4. Picard M, Wallace DC, Burelle Y. The rise of mitochondria in medicine. Mitochondrion. 2016;30:105–16.

    Article  CAS  Google Scholar 

  5. Mishmar D, Ruiz-Pesini E, Golik P, Macaulay V, Clark AG, Hosseini S, et al. Natural selection shaped regional mtDNA variation in humans. Proc Natl Acad Sci USA. 2003;100:171–6.

    Article  CAS  Google Scholar 

  6. Veronese N, Stubbs B, Solmi M, Vaona A, Demurtas J, Carvalho AF, et al. Mitochondrial genetic haplogroups and depressive symptoms: A large study among people in North America. J Affect Disord. 2017;217:55–9.

    Article  Google Scholar 

  7. Wortmann SB, Zweers-van Essen H, Rodenburg RJ, van den Heuvel LP, de Vries MC, Rasmussen-Conrad E, et al. Mitochondrial energy production correlates with the age-related BMI. Pediatr Res. 2009;65:103–8.

    Article  CAS  Google Scholar 

  8. Yang TL, Guo Y, Shen H, Lei SF, Liu YJ, Li J, et al. Genetic association study of common mitochondrial variants on body fat mass. PLoS ONE. 2011;6:e21595.

    Article  CAS  Google Scholar 

  9. Nardelli C, Labruna G, Liguori R, Mazzaccara C, Ferrigno M, Capobianco V, et al. Haplogroup T is an obesity risk factor: mitochondrial DNA haplotyping in a morbid obese population from southern Italy. BioMed Res Int. 2013;2013:631082.

    Article  Google Scholar 

  10. Ebner S, Mangge H, Langhof H, Halle M, Siegrist M, Aigner E, et al. Mitochondrial Haplogroup T is associated with obesity in austrian juveniles and adults. PLoS One 2015;10:e0135622.

    Article  Google Scholar 

  11. Grant SF, Glessner JT, Bradfield JP, Zhao J, Tirone JE, Berkowitz RI, et al. Lack of relationship between mitochondrial heteroplasmy or variation and childhood obesity. Int J Obes (Lond). 2012;36:80–3.

    Article  CAS  Google Scholar 

  12. Rego-Perez I, Fernandez-Moreno M, Fernandez-Lopez C, Arenas J, Blanco FJ. Mitochondrial DNA haplogroups: role in the prevalence and severity of knee osteoarthritis. Arthritis Rheum. 2008;58:2387–96.

    Article  CAS  Google Scholar 

  13. Torroni A, Huoponen K, Francalacci P, Petrozzi M, Morelli L, Scozzari R, et al. Classification of European mtDNAs from an analysis of three European populations. Genetics. 1996;144:1835–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Marty CB, Marie TL, Kevin CN, Syawal S, Shamkant BN, Pierre B, Douglas CW. MITOMAP: a human mitochondrial genome database—2004 update. Nucleic Acids Research. 2005;33:D611–D613.

    Article  Google Scholar 

  15. Fernandez-Caggiano M, Barallobre-Barreiro J, Rego-Perez I, Crespo-Leiro MG, Paniagua MJ, Grille Z, et al. Mitochondrial haplogroups H and J: risk and protective factors for ischemic cardiomyopathy. PLoS ONE. 2012;7:e44128.

    Article  CAS  Google Scholar 

  16. WHO Consultation on Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organization technical report series, Geneva 1–253; 894: i–xii, 2000.

  17. Washburn RA, McAuley E, Katula J, Mihalko SL, Boileau RA. The physical activity scale for the elderly (PASE): evidence for validity. J Clin Epidemiol. 1999;52:643–51.

    Article  CAS  Google Scholar 

  18. Veronese N, Stubbs B, Noale M, Solmi M, Vaona A. demurtas J, et al. Fried potato consumption is associated with elevated mortality: an 8-year longitudinal cohort study. Am J Clin Nutr. 2017;106:162–67.

    Article  CAS  Google Scholar 

  19. Ruiz-Pesini E, Mishmar D, Brandon M, Procaccio V, Wallace DC. Effects of purifying and adaptive selection on regional variation in human mtDNA. Science. 2004;303:223–6.

    Article  CAS  Google Scholar 

  20. Hulgan T, Haubrich R, Riddler SA, Tebas P, Ritchie MD, McComsey GA, et al. European mitochondrial DNA haplogroups and metabolic changes during antiretroviral therapy in AIDS Clinical Trials Group Study A5142. AIDS. 2011;25:37–47.

    Article  CAS  Google Scholar 

  21. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980– 2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384:766–81.

    Article  Google Scholar 

  22. Herrera BM, Lindgren CM. The genetics of obesity. Curr Diab Rep. 2010;10:498–505.

    Article  CAS  Google Scholar 

  23. Emilsson V, Thorleifsson G, Zhang B, Leonardson AS, Zink F, Zhu J, et al. Genetics of gene expression and its effect on disease. Nature. 2008;452:423–8.

    Article  CAS  Google Scholar 

  24. Hill JO, Wyatt HR, Peters JC. Energy balance and obesity. Circulation. 2012;126:126–32.

    Article  Google Scholar 

  25. Hamilton MT, Hamilton DG, Zderic TW. Role of low energy expenditure and sitting in obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease. Diabetes. 2007;56:2655–67.

    Article  CAS  Google Scholar 

  26. Barnes AS. Obesity and sedentary lifestyles: Risk for cardiovascular disease in women. Tex Heart Inst J. 2012;39:224–7.

    PubMed  PubMed Central  Google Scholar 

  27. Caudwell P, Gibbons C, Finlayson G, Näslund E, Blundell J. Physical activity, energy intake, and obesity: The links between exercise and appetite. Curr Obes Rep. 2013;2:185–90.

    Article  Google Scholar 

  28. Bradfield JP, Taal HR, Timpson NJ, Scherag A, Lecoeur C, Warrington NM, et al. A genome-wide association meta-analysis identifies new childhood obesity loci. Nat Genet. 2012;44:526–31.

    Article  CAS  Google Scholar 

  29. Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518:197–206.

    Article  CAS  Google Scholar 

  30. Hu F. Obesity epidemiology. (New York, Oxford University Press, 2008).

  31. Pea A, Yu J, Rezaee N, et al. Targeted DNA sequencing reveals pattern of local progression in the pancreatic remnant following resection of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Ann Surg. 2017;266:133–141.

    Article  Google Scholar 

  32. Yachida S, Wood LD, Suzuki M, et al. Genomic sequencing identifies ELF3 as a driver of ampullary carcinoma. Cancer Cell. 2016;29:229–240.

    Article  CAS  Google Scholar 

  33. Saki M, Prakash A. DNA damage related crosstalk between the nucleus and mitochondria. Free Radic Biol Med. 2017;107:216–227.

    Article  CAS  Google Scholar 

  34. Meschia JF, Ross OA. Does mitochondrial DNA have a protective role in stroke? Lancet Neurol. 2010;9:453–4.

    Article  Google Scholar 

Download references

Funding

The OAI is funded by the National Institute of Health. Private funding partners include Merck Research Laboratories; Novartis Pharmaceuticals Corporation, GlaxoSmithKline; and Pfizer, Inc. Private sector funding for the OAI is managed by the Foundation for the National Institutes of Health. This manuscript was prepared using an OAI public use data set and does not necessarily reflect the opinions or views of the OAI investigators, the NIH, or the private funding partners. Funding sources had no role in study design, data treatment, or report writing.

Author information

Authors and Affiliations

  1. National Research Council, Neuroscience Institute, Aging Branch, Padova, Italy

    Nicola Veronese & Stefania Maggi

  2. Ambulatory of Nutrition, IRCCS “S. de Bellis”, National Institute of Gastroenterology-Research Hospital, Castellana Grotte, Bari, Italy

    Nicola Veronese

  3. South London and Maudsley NHS Foundation Trust, London, UK

    Brendon Stubbs

  4. Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, UK

    Brendon Stubbs

  5. Faculty of Health, Social Care and Education, Anglia Ruskin University, Chelmsford, UK

    Brendon Stubbs & Patricia Schofield

  6. Research and Development Unit, Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, CIBERSAM, Sant Boi de Llobregat, Barcelona, Spain

    Ai Koyanagi

  7. Primary Care Department, Azienda ULSS20 Verona, Verona, Italy

    Alberto Vaona

  8. Primary Care Department, Azienda USL Toscana Sud Est, Grosseto, Italy

    Jacopo Demurtas

  9. Faculty of Education and Health, University of Greenwich, London, UK

    Trevor Thompson

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  1. Nicola Veronese
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Correspondence to Nicola Veronese.

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Veronese, N., Stubbs, B., Koyanagi, A. et al. Mitochondrial genetic haplogroups and incident obesity: a longitudinal cohort study. Eur J Clin Nutr 72, 587–592 (2018). https://doi.org/10.1038/s41430-018-0097-y

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