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

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.

SUBMITTER: Snogdal LS

PROVIDER: S-EPMC4231429 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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

Snogdal Lena Sønder LS Grarup Niels N Banasik Karina K Wod Mette M Jørgensen Torben T Witte Daniel R DR Lauritzen Torsten T Nielsen Aneta A AA Brandslund Ivan I Christensen Cramer C Pedersen Oluf O Yderstræde Knud K Beck-Nielsen Henning H Henriksen Jan Erik JE Hansen Torben T Højlund Kurt K

BMC medical genetics 20131025

<h4>Background</h4>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 ...[more]

PMID: 24156295

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Dataset Information

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

Publications

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

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