A null mutation in ANGPTL8 does not associate with either plasma glucose or type 2 diabetes in humans
Year: 2016
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Experiments in mice initially suggested a role for the protein angiopoietin-like 8 (ANGPTL8) in glucose homeostasis. However, subsequent experiments in model systems have challenged this proposed role. We sought to better understand the importance of ANGPTL8 in human glucose homeostasis by examining the association of a null mutation in ANGPTL8 with fasting glucose levels and risk for type 2 diabetes. METHODS: A naturally-occurring null mutation in human ANGPTL8 (rs145464906; c.361C > T; p.Q121X) is carried by ~1 in 1000 individuals of European ancestry and is associated with higher levels of plasma high-density lipoprotein cholesterol, suggesting that this mutation has functional significance. We examined the association of p.Q121X with fasting glucose levels and risk for type 2 diabetes in up to 95,558 individuals (14,824 type 2 diabetics and 80,734 controls). RESULTS: We found no significant association of p.Q121X with either fasting glucose or type 2 diabetes (p-value = 0.90 and 0.65, respectively). Given our sample sizes, we had >98 % power to detect at least a 0.23 mmol/L effect on plasma glucose and >95 % power to detect a 70 % increase in risk for type 2 diabetes. CONCLUSION: Disruption of ANGPTL8 function in humans does not seem to have a large effect on measures of glucose tolerance.
Source: BMC Endocrine Disorders
Institutions: Harvard University, Massachusetts General Hospital, Brigham and Women's Hospital, National Heart, Lung, and Blood Institute, Framingham Heart Study, Indiana University Indianapolis, Indiana University School of Medicine, Broad Institute, Icahn School of Medicine at Mount Sinai, University of Cambridge, MRC Epidemiology Unit, University of Pennsylvania, University of Michigan, Centre for Human Genetics, Churchill Hospital, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,190
Funders: Massachusetts General Hospital, Donovan Family Foundation, National Institute for Health and Care Research, Fondation Leducq, National Institutes of Health, Medical Research Council, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences
Awards: Indiana Clinical and Translational Sciences Institute, Identifying Genes for Type 2 Diabetes: FUSION, G3812975344, G385201875, Discovering lipoprotein lipase pathway variants that protect against CHD, G5413383169, NIHR Senior Investigator Award, G6957823285, Discovery of Mendelian Dyslipidemia and Heart Attack Genes Using Exome Sequencing, Michigan Diabetes Research Center (MDRC), Integrated, Multidisciplinary Training in Cardiovascular Research
OpenAlex ID: W2280038725