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Open Access Research article

Studies of association of AGPAT6 variants with type 2 diabetes and related metabolic phenotypes in 12,068 Danes

Lena Sønder Snogdal12*, Niels Grarup3, Karina Banasik3, Mette Wod12, Torben Jørgensen45, Daniel R Witte6, Torsten Lauritzen7, Aneta A Nielsen8, Ivan Brandslund89, Cramer Christensen10, Oluf Pedersen11123, Knud Yderstræde1, Henning Beck-Nielsen1, Jan Erik Henriksen1, Torben Hansen23 and Kurt Højlund12

Author Affiliations

1 Department of Endocrinology, Diabetes Research Center, Odense University Hospital, Odense, Denmark

2 Section of Molecular Diabetes & Metabolism, Institute of Clinical Research & Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark

3 The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

4 Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark

5 Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

6 Steno Diabetes Center, Gentofte, Denmark

7 Department of General Practice, University of Aarhus, Aarhus, Denmark

8 Department of Clinical Biochemistry, Vejle Hospital, Vejle, Denmark

9 Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark

10 Department of Internal Medicine and Endocrinology, Vejle Hospital, Vejle, Denmark

11 Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark

12 Hagedorn Research Institute, Gentofte, Denmark

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BMC Medical Genetics 2013, 14:113  doi:10.1186/1471-2350-14-113

Published: 25 October 2013

Abstract

Background

Type 2 diabetes, obesity and insulin resistance are characterized by hypertriglyceridemia and ectopic accumulation of lipids in liver and skeletal muscle. AGPAT6 encodes a novel glycerol-3 phosphate acyltransferase, GPAT4, which catalyzes the first step in the de novo triglyceride synthesis. AGPAT6-deficient mice show lower weight and resistance to diet- and genetically induced obesity. Here, we examined whether common or low-frequency variants in AGPAT6 associate with type 2 diabetes or related metabolic traits in a Danish population.

Methods

Eleven variants selected by a candidate gene approach capturing the common and low-frequency variation of AGPAT6 were genotyped in 12,068 Danes from four study populations of middle-aged individuals. The case–control study involved 4,638 type 2 diabetic and 5,934 glucose-tolerant individuals, while studies of quantitative metabolic traits were performed in 5,645 non-diabetic participants of the Inter99 Study.

Results

None of the eleven AGPAT6 variants were robustly associated with type 2 diabetes in the Danish case–control study. Moreover, none of the AGPAT6 variants showed association with measures of obesity (waist circumference and BMI), serum lipid concentrations, fasting or 2-h post-glucose load levels of plasma glucose and serum insulin, or estimated indices of insulin secretion or insulin sensitivity.

Conclusions

Common and low-frequency variants in AGPAT6 do not significantly associate with type 2 diabetes susceptibility, or influence related phenotypic traits such as obesity, dyslipidemia or indices of insulin sensitivity or insulin secretion in the population studied.

Keywords:
Type 2 diabetes; Genetics; Insulin resistance; Human; Lipid droplets; AGPAT6; GPAT4