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Current Diabetes Reports

Erschienen in:

01.09.2017 | Genetics (AP Morris, Section Editor)

Mechanisms of Type 2 Diabetes Risk Loci

verfasst von: Kyle J. Gaulton

Erschienen in: Current Diabetes Reports | Ausgabe 9/2017

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Abstract

Purpose of Review

Deciphering the mechanisms of type 2 diabetes (T2DM) risk loci can greatly inform on disease pathology. This review discusses current knowledge of mechanisms through which genetic variants influence T2DM risk and considerations for future studies.

Recent Findings

Over 100 T2DM risk loci to date have been identified. Candidate causal variants at risk loci map predominantly to non-coding sequence. Physiological, epigenomic and gene expression data suggest that variants at many known T2DM risk loci affect pancreatic islet regulation, although variants at other loci also affect protein function and regulatory processes in adipose, pre-adipose, liver, skeletal muscle and brain. The effects of T2DM variants on regulatory activity in these tissues appear largely, but not exclusively, due to altered transcription factor binding. Putative target genes of T2DM variants have been defined at an increasing number of loci and some, such as FTO, may entail several genes and multiple tissues. Gene networks in islets and adipocytes have been implicated in T2DM risk, although the molecular pathways of risk genes remain largely undefined.

Summary

Efforts to fully define the mechanisms of T2DM risk loci are just beginning. Continued identification of risk mechanisms will benefit from combining genetic fine-mapping with detailed phenotypic association data, high-throughput epigenomics data from diabetes-relevant tissue, functional screening of candidate genes and genome editing of cellular and animal models.

Worth Health Organiziation. www.who.int/mediacentre/factsheets/fs312/en/. Accessed July 2017.

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Titel: Mechanisms of Type 2 Diabetes Risk Loci
verfasst von: Kyle J. Gaulton
Publikationsdatum: 01.09.2017
Verlag: Springer US
Erschienen in: Current Diabetes Reports / Ausgabe 9/2017
Print ISSN: 1534-4827
Elektronische ISSN: 1539-0829
DOI: https://doi.org/10.1007/s11892-017-0908-x

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