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

BMC Medical Genetics

Kurt Højlund⁴  Torben Hansen³  Jan Erik Henriksen⁵  Henning Beck-Nielsen⁵  Knud Yderstræde⁵  Oluf Pedersen³  Cramer Christensen⁹  Ivan Brandslund⁷  Aneta A Nielsen²  Torsten Lauritzen¹  Daniel R Witte⁸  Torben Jørgensen⁶  Mette Wod⁴  Karina Banasik³  Niels Grarup³  Lena Sønder Snogdal⁴ 

[1] Department of General Practice, University of Aarhus, Aarhus, Denmark;Department of Clinical Biochemistry, Vejle Hospital, Vejle, Denmark;The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;Section of Molecular Diabetes & Metabolism, Institute of Clinical Research & Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark;Department of Endocrinology, Diabetes Research Center, Odense University Hospital, Odense, Denmark;Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark;Steno Diabetes Center, Gentofte, Denmark;Department of Internal Medicine and Endocrinology, Vejle Hospital, Vejle, Denmark

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

Others  :  1122591
DOI  :  10.1186/1471-2350-14-113

 received in 2013-02-18, accepted in 2013-10-21,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Snogdal et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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