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Epigenetic Epidemiology of Type 1 Diabetes

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Epigenetic Epidemiology

Abstract

Type 1 diabetes (T1D) results from the immune-mediated destruction of insulin-secreting β-cells that reside in the pancreatic Islets of Langerhans. Genetic susceptibility is necessary but not sufficient for the development of autoimmune diabetes, indicating a key role for risk modification by environmental factors. Epigenetic mechanisms could mediate the effect of specific environmental factors and could therefore explain, at least in part, non-genetic susceptibility to Type 1 diabetes. Exposure to variable nutrition or infection in early life, including in utero experiences can modify T1D susceptibility, which may occur via epigenetic means. T1D is characterized by autoimmune destruction of pancreatic insulin-secreting β-cells and their aberrant development and function of β-cells; these pathogenic mechanisms are also subject to epigenetic regulation. Furthermore, the diabetic state, characterized by fluctuations in insulin and glucose, can influence genomic methylation profiles and gene expression, which can potentially impact susceptibility to co-morbidities of T1D. This chapter identifies potential epigenetic mechanisms that may modify T1D risk and describes study designs that can be implemented to determine the role played by epigenetics in disease pathogenesis.

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Abbreviations

AdoMet:

S-adenosylmethionine

AdoHcy:

S-adenosylhomocysteine

BMI:

Body mass index

CBS:

Cystathionine β-synthase

ChIP:

Chromatin immunoprecipitation

DAISY:

Diabetes Autoimmunity Study in the Young

DIPP:

Diabetes Prediction and Prevention

DNMT:

DNA methyltransferase

HLA:

Human leukocyte antigen

IFN:

Interferon

IL:

Interleukin

LFA:

Lymphocyte function-associated antigen

MHC:

Major histocompatibility complex

MS:

Methionine synthase

NF-κB:

Nuclear factor-κB

Seq:

Sequencing

SNP:

Single nucleotide polymorphism

TCR:

T cell receptor

TEDDY:

The Environmental Determinants of Diabetes in the Young

TH :

T helper

T1D:

Type 1 diabetes

Treg :

T regulatory

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Acknowledgments

The author would like to thank Alfred Aziz, Fraser Scott and Alex Wong for helpful discussions. This work is funded by Health Canada.

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Authors and Affiliations

  1. Department of Biology, Faculty of Science, Carleton University, Ottawa, ON, Canada

    Amanda J. MacFarlane

  2. Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada

    Amanda J. MacFarlane

  3. Nutrition Research Division, Food Directorate, Health Canada, 251 Sir Frederick Banting Drive, Ottawa, ON, K1A 0K9, Canada

    Amanda J. MacFarlane

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  1. Amanda J. MacFarlane
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Correspondence to Amanda J. MacFarlane .

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  1. , Obstetrics and Gynecology Epidemiology D, Brigham and Women’s Hospital, Longwood Avenue 221, Boston, 02115, Massachusetts, USA

    Karin B. Michels

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MacFarlane, A.J. (2012). Epigenetic Epidemiology of Type 1 Diabetes. In: Michels, K. (eds) Epigenetic Epidemiology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2495-2_19

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