Cited by 83Diabetes and associated disordersGenetic Associations and EpidemiologyMultiple Sclerosis Research Studies

The genetic basis for type 1 diabetes

Mehers, K. L., Gillespie, K. M.·2008·British Medical Bulletin

Abstract

BACKGROUND: Type 1 diabetes (T1D) is characterized by autoimmune destruction of insulin-producing beta-cells in the pancreas resulting from the action of environmental factors on genetically predisposed individuals. The increasing incidence over recent decades remains unexplained, but the capacity of identifying infants at highest genetic risk has become an increasing requirement for potential therapeutic intervention trials. SOURCES OF DATA: Literature searches on T1D and genes were carried out, and key papers since the 1970s were highlighted for inclusion in this review. AREAS OF AGREEMENT: Early genetic studies identified the most important region for genetic susceptibility to T1D-the human leukocyte antigen genes on chromosome 6; later shown to contribute approximately half of the genetic determination of T1D. The other half is made up of multiple genes, each having a limited individual impact on genetic susceptibility. AREAS OF CONTROVERSY: Historically, there have been many controversial genetic associations with T1D, mostly caused by underpowered case-control studies but these are now decreasing in frequency. AREAS OF GROWTH: The functional effect of each gene associated with T1D must be investigated to determine its usefulness both in risk assessment and as a potential therapeutic target. AREAS TIMELY FOR DEVELOPING RESEARCH: Recently identified copy number variants in DNA and epigenetic modifications (heritable changes not associated with changes in the DNA sequence) are also likely to play a role in genetic susceptibility to T1D.

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Crossref · 10.1093/bmb/ldn045

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81 of 81 references verified0 citation errors · 0 not checkable

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  • The most important genes implicated in type 1 diabetes susceptibility and resistance are in the HLA complex on chromosome 6, particularly HLA class II.

    “Of the multiple genes implicated in susceptibility (and resistance) to T1D, the most important are the human leukocyte antigen (HLA) complex on chromosome 6, in particular the HLA class II.”

    From Epidemiology of type 1 diabetes (2010) · cites this paper as [41]

  • Two susceptibility haplotypes in the HLA class II region are now considered the principal susceptibility markers for type 1 diabetes.

    “Two susceptibility haplotypes in the HLA class II region are now considered the principal susceptibility markers for T1D41.”

    From Epidemiology of type 1 diabetes (2010) · cites this paper as [41]

  • The remaining genetic risk in type 1 diabetes is made up of many diverse genes, each with a small individual impact on genetic susceptibility.

    “The remaining genetic risk is made up of many diverse genes, each having a small individual impact on genetic susceptibility41.”

    From Epidemiology of type 1 diabetes (2010) · cites this paper as [41]

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Authors
Mehers, K. L., & Gillespie, K. M.
Affiliations
  • Southmead Hospital (GB)
  • University of Bristol (GB)
Corresponding author
Gillespie, K. M.
Venue
British Medical Bulletin
Published
2008-12-05
Volume
88
Issue
1
Pages
115-129
ISSN
  • 0007-1420 (ISSN-L)
  • 1471-8391
OpenAlex
W2140903224
Cited by
83
References
80
Citations by year
2025: 1 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 8 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 2 · 2016: 5 · 2015: 7 · 2014: 7 · 2013: 8 · 2012: 9
FWCI
0.45
Type
journal article
Language
en
Open access
closed
Locations
  • British Medical Bulletin (publishedVersion)
  • PubMed (publishedVersion)
  • Bristol Research (University of Bristol) (publishedVersion)
Funders
University of Bristol
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
Keywords
type 1 diabetes, genetic susceptibility, HLA genes, chromosome 6, islet autoimmunity, genetic association studies, copy number variation, epigenetic modifications, risk prediction, therapeutic target
MeSH terms
Autoantibodies, Diabetes Mellitus, Type 1, Genes, HLA Antigens, Humans, Infant, Insulin, Islets of Langerhans, Risk Factors, Autoimmunity, Genetic Predisposition to Disease

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