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A single-nucleotide polymorphism in the MicroRNA-146a gene is associated with diabetic nephropathy and sight-threatening diabetic retinopathy in Caucasian patients

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Abstract

Aims

This study aimed to investigate whether the single-nucleotide polymorphism (SNP) rs2910164 residing within microRNA-146a (miR-146a) is associated with diabetic microvascular complications diabetic nephropathy (DN), proliferative diabetic retinopathy (PDR) or diabetic macular oedema (DME) in either Caucasian patients with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus.

Methods

Caucasian patients with T1DM (n = 733) or T2DM (n = 2215) were recruited from ophthalmology, renal and endocrine clinics in Australia and the UK. Patients with T2DM were required to have diabetes mellitus (DM) for at least 5 years and be on treatment with oral hypoglycaemic drugs or insulin. In total, 890 participants had DN (168 with T1DM and 722 with T2DM), 731 had PDR (251 with T1DM and 480 with T2DM) and 1026 had DME (170 with T1DM and 856 with T2DM). Participants were genotyped for SNP rs2910164 in miR-146a. Analyses investigating association were adjusted for relevant clinical covariates including age, sex, DM duration, HbA1c and hypertension.

Results

A significant association was found between the C allele of rs2910164 and DN in the T1DM group (OR 1.93; CI 1.23–3.03; P = 0.004), but no association found in the T2DM group (OR 1.05; CI 0.83–1.32; P = 0.691). In the subset of T2DM patients, the C allele was specifically associated with DME (OR 1.25; CI 1.03–1.53; P = 0.025). No association with DME was found in the T1DM group (OR 0.87; CI 0.54–1.42); P = 0.583), or with PDR for either type of DM.

Conclusions

Rs2910164 is significantly associated with microvascular complications DN in patients with T1DM and DME in patients with T2DM.

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Acknowledgments

This work was funded by a National Health and Medical Research Council (NHMRC) of Australia project Grant (#595918), the National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology. The sponsor or funding organisation had no role in the design or conduct of this research. GK is funded by an NHMRC Clinical Research Postgraduate Scholarship and an Avant Doctor in Training Research Scholarship. Jamie Craig is supported in part by an NHMRC Practitioner Fellowship and Kathryn Burdon by an NHMRC Senior Research Fellowship.

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Authors and Affiliations

  1. Department of Ophthalmology, Flinders Medical Centre, Flinders University, GPO Box 2100, Adelaide, SA, 5001, Australia

    Georgia Kaidonis, Sotoodeh Abhary, Ebony Liu, Stewart Lake, Jamie E. Craig & Kathryn P. Burdon

  2. Save Sight Institute, Clinical Ophthalmology and Eye Health, The University of Sydney, Sydney, NSW, Australia

    Mark C. Gillies

  3. Academic Unit of Ophthalmology, Australian National University, Canberra, Australia

    Rohan W. Essex

  4. School of Medical Sciences, University of NSW, Sydney, NSW, Australia

    John H. Chang

  5. Medical Retina Service, Moorfields Eye Hospital, London, UK

    John H. Chang, Bishwanath Pal, Sobha Sivaprasad & Maria Pefkianaki

  6. Department of Ophthalmology, Royal Melbourne Hospital, Melbourne, VIC, Australia

    Mark Daniell

  7. Department of Endocrinology, Flinders Medical Centre, Flinders University, Adelaide, SA, Australia

    Nikolai Petrovsky

  8. Centre for Eye Research Australia, University of Melbourne, Melbourne, VIC, Australia

    Alex W. Hewitt & Ecosse L. Lamoureux

  9. St Vincent’s Hospital, Melbourne, VIC, Australia

    Alicia Jenkins

  10. Singapore Eye Research Institute, Singapore, Singapore

    Ecosse L. Lamoureux

  11. Department of Renal Medicine, Flinders Medical Centre, Flinders University, Adelaide, SA, Australia

    Jonathan M. Gleadle

  12. Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia

    Kathryn P. Burdon

Authors
  1. Georgia Kaidonis
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  2. Mark C. Gillies
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  3. Sotoodeh Abhary
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  4. Ebony Liu
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  6. John H. Chang
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  7. Bishwanath Pal
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  9. Maria Pefkianaki
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  10. Mark Daniell
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  11. Stewart Lake
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  13. Alex W. Hewitt
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  14. Alicia Jenkins
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  15. Ecosse L. Lamoureux
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  16. Jonathan M. Gleadle
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  17. Jamie E. Craig
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  18. Kathryn P. Burdon
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Corresponding author

Correspondence to Georgia Kaidonis.

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The authors declare that they have no conflict of interest.

Ethical standard

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5).

Human and animal rights

This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all patients for being included in the study.

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Managed by Massimo Federici.

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Kaidonis, G., Gillies, M.C., Abhary, S. et al. A single-nucleotide polymorphism in the MicroRNA-146a gene is associated with diabetic nephropathy and sight-threatening diabetic retinopathy in Caucasian patients. Acta Diabetol 53, 643–650 (2016). https://doi.org/10.1007/s00592-016-0850-4

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  • DOI: https://doi.org/10.1007/s00592-016-0850-4

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