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Association between large detectable clonal mosaicism and type 2 diabetes with vascular complications

Nature Genetics volume 45, pages 10401043 (2013) | Download Citation

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Abstract

Large chromosomal clonal mosaic events (CMEs) have been suggested to be linked to aging1,2,3 and to predict cancer2,3. Type 2 diabetes (T2D) has been conceptualized as an accelerated-aging disease4,5,6 and is associated with higher prevalence of cancers7,8,9,10,11. Here we aimed to assess the association between T2D and CME occurrence in blood. We evaluated the presence of CMEs in 7,659 individuals (including 2,208 with T2D) using DNA arrays. A significant association between CME occurrence and T2D was found (odds ratio (OR) = 5.3; P = 5.1 × 10−5) and was stronger when we only considered non-obese individuals with T2D (OR = 5.6; P = 4.9 × 10−5). Notably, CME carriers with T2D had higher prevalence of vascular complications than non-carriers with T2D (71.4% versus 37.1%, respectively; P = 7.7 × 10−4). In CME carriers, we found an increase in the percentage of abnormal cells over 6 years (P = 8.60 × 10−3). In conclusion, given the increased risk of cancer in CME carriers2,3, our results may have profound clinical implications in patients with severe T2D.

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Acknowledgements

We are sincerely indebted to all participants in the genetic study. We thank M. Deweirder and F. Allegaert for their technical assistance and their invaluable management of DNA samples. This study was supported by the Contrat de Projets Etat–Région Nord-Pas-De-Calais (CPER Axe Cardio-Diabète to P.F.), the Délégation Régionale à la Recherche et à la Technologie de la Région Nord-Pas-De-Calais (DRRT), the European Union (Fonds Européen de Développement Régional (FEDER)) and the Centre National de la Recherche Scientifique (CNRS).

Author information

Author notes

    • Boris Skrobek
    •  & Stéphane Lobbens

    These authors contributed equally to this work.

Affiliations

  1. Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 8199, Lille Pasteur Institute, Lille, France.

    • Amélie Bonnefond
    • , Boris Skrobek
    • , Stéphane Lobbens
    • , Elodie Eury
    • , Dorothée Thuillier
    • , Stéphane Cauchi
    • , Loïc Yengo
    •  & Philippe Froguel
  2. Lille II University, Lille, France.

    • Amélie Bonnefond
    • , Boris Skrobek
    • , Stéphane Lobbens
    • , Elodie Eury
    • , Dorothée Thuillier
    • , Stéphane Cauchi
    • , Loïc Yengo
    •  & Philippe Froguel
  3. European Genomic Institute for Diabetes (EGID), Lille, France.

    • Amélie Bonnefond
    • , Boris Skrobek
    • , Stéphane Lobbens
    • , Elodie Eury
    • , Dorothée Thuillier
    • , Stéphane Cauchi
    • , Loïc Yengo
    •  & Philippe Froguel
  4. Institut Inter-Régional pour la Santé (IRSA), La Riche, France.

    • Olivier Lantieri
  5. Institut National de la Santé et de la Recherche Médicale (INSERM) U1018, Centre for Research in Epidemiology and Population Health, Villejuif, France.

    • Beverley Balkau
  6. University Paris–Sud, Villejuif, France.

    • Beverley Balkau
  7. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.

    • Elio Riboli
  8. Department of Endocrinology, Diabetology and Nutrition, Bichat-Claude Bernard University Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), Paris, France.

    • Michel Marre
  9. INSERM U695, Paris 7 University, Paris, France.

    • Michel Marre
  10. Department of Endocrinology and Diabetology, Corbeil-Essonnes Hospital, Essonnes, France.

    • Guillaume Charpentier
  11. Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London, UK.

    • Philippe Froguel
  12. Qatar Biomedical Research Institute (QBRI), Doha, Qatar.

    • Philippe Froguel

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Contributions

A.B. and P.F. designed the study and wrote the manuscript. B.S. and L.Y. performed the statistical analyses (CME detection and association analyses) and contributed to writing the manuscript. A.B. contributed to the statistical analyses. S.L. and E.E. performed the genotyping. D.T. contributed to the genotyping. S.C., O.L., B.B., E.R., M.M., G.C. and P.F. contributed to cohort study samples and researched data. All authors approved and commented on the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Philippe Froguel.

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DOI

https://doi.org/10.1038/ng.2700

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