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Published on: January 7, 2018
Variants in MTNR1B influence fasting glucose levels.
Inga Prokopenko1, Claudia Langenberg, Jose C Florez
1[1] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK. [2] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. [3] These authors contributed equally to this work.
Nature Genetics
|December 9, 2008
Summary
Genetic variants in the MTNR1B gene significantly impact fasting glucose levels and beta-cell function. This finding links melatonin receptor 1B to an increased risk of type 2 diabetes in European populations.
Area of Science:
- Human Genetics
- Metabolic Disorders
- Molecular Endocrinology
Background:
- Fasting glucose is a key indicator of metabolic health and a predictor of diabetes risk.
- Genome-wide association studies (GWAS) have identified several genetic loci associated with fasting glucose, but many more likely remain undiscovered.
Purpose of the Study:
- To identify novel genetic loci associated with fasting glucose concentrations.
- To investigate the functional impact of identified variants on beta-cell function and type 2 diabetes risk.
Main Methods:
- Meta-analysis of ten genome-wide association scans (N=36,610) in individuals of European descent.
- Association testing of variants with fasting glucose, beta-cell function (HOMA-B), and type 2 diabetes risk.
- Replication in a large meta-analysis of case-control studies for type 2 diabetes.
Main Results:
- Variants in the melatonin receptor 1B (MTNR1B) gene, specifically rs10830963, were consistently associated with higher fasting glucose levels.
- The G allele of rs10830963 was linked to reduced beta-cell function and an increased risk of type 2 diabetes.
- Previous associations with G6PC2 and GCK loci were confirmed.
Conclusions:
- The MTNR1B gene plays a significant role in regulating glucose metabolism and insulin secretion.
- Genetic variations in MTNR1B represent a novel risk factor for type 2 diabetes.
- These findings highlight MTNR1B as a potential therapeutic target for managing glucose homeostasis.
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