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BMC Endocr Disord. 2016 Jan 28;16:7. doi: 10.1186/s12902-016-0088-8.

A null mutation in ANGPTL8 does not associate with either plasma glucose or type 2 diabetes in humans.

Author information

1
Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
2
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, 02215, USA.
3
National Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study, Framingham, MA, 01702, USA.
4
Department of Epidemiology, Fairbanks School of Public Health, Indianapolis, IN, 46202, USA.
5
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
6
Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, 02114, USA.
7
Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, 02114, USA.
8
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, 02142, USA.
9
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, 02114, USA.
10
Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
11
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0SL, UK.
12
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
13
Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
14
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
15
Oxford Centre for Diabetes, Endocrinology, and Metabolism, Churchill Hospital, University of Oxford, Oxford, UK.
16
Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK.
17
Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA.
18
Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA. gpeloso@bu.edu.
19
Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, 02114, USA. gpeloso@bu.edu.
20
Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, 02114, USA. gpeloso@bu.edu.
21
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, 02142, USA. gpeloso@bu.edu.
22
, 801 Massachusetts Ave, Crosstown Center, Third Floor, Boston, MA, 02118, USA. gpeloso@bu.edu.

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.

PMID:
26822414
PMCID:
PMC4730725
DOI:
10.1186/s12902-016-0088-8
[Indexed for MEDLINE]
Free PMC Article

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