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

Lena Sønder Snogdal; Niels Grarup; Karina Banasik; Mette Wod; Torben Jørgensen; Daniel R Witte; Torsten Lauritzen; Aneta Aleksandra Nielsen; Ivan Brandslund; Cramer Christensen; Oluf Pedersen; Knud Bonnet Yderstræde; Henning Beck-Nielsen; Jan Erik Henriksen; Torben Hansen; Kurt Højlund

doi:10.1186/1471-2350-14-113

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

Lena Sønder Snogdal, Niels Grarup, Karina Banasik, Mette Wod, Torben Jørgensen, Daniel R Witte, Torsten Lauritzen, Aneta Aleksandra Nielsen, Ivan Brandslund, Cramer Christensen, Oluf Pedersen, Knud Bonnet Yderstræde, Henning Beck-Nielsen, Jan Erik Henriksen, Torben Hansen, Kurt Højlund

Department of Public Health

1 Citation (Scopus)

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.

Original language	English
Journal	BMC Medical Genetics
Volume	14
Issue number	1
Pages (from-to)	113
ISSN	1471-2350
DOIs	https://doi.org/10.1186/1471-2350-14-113
Publication status	Published - 25 Oct 2013

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Snogdal, L. S., Grarup, N., Banasik, K., Wod, M., Jørgensen, T., Witte, D. R., Lauritzen, T., Nielsen, A. A., Brandslund, I., Christensen, C., Pedersen, O., Yderstræde, K. B., Beck-Nielsen, H., Henriksen, J. E., Hansen, T., & Højlund, K. (2013). Studies of association of AGPAT6 variants with type 2 diabetes and related metabolic phenotypes in 12,068 Danes. BMC Medical Genetics, 14(1), 113. https://doi.org/10.1186/1471-2350-14-113

Snogdal, LS, Grarup, N , Banasik, K, Wod, M, Jørgensen, T, Witte, DR, Lauritzen, T, Nielsen, AA, Brandslund, I, Christensen, C, Pedersen, O, Yderstræde, KB, Beck-Nielsen, H, Henriksen, JE, Hansen, T & Højlund, K 2013, 'Studies of association of AGPAT6 variants with type 2 diabetes and related metabolic phenotypes in 12,068 Danes', BMC Medical Genetics, vol. 14, no. 1, pp. 113. https://doi.org/10.1186/1471-2350-14-113

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title = "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.",

author = "Snogdal, {Lena S{\o}nder} and Niels Grarup and Karina Banasik and Mette Wod and Torben J{\o}rgensen and Witte, {Daniel R} and Torsten Lauritzen and Nielsen, {Aneta Aleksandra} and Ivan Brandslund and Cramer Christensen and Oluf Pedersen and Yderstr{\ae}de, {Knud Bonnet} and Henning Beck-Nielsen and Henriksen, {Jan Erik} and Torben Hansen and Kurt H{\o}jlund",

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doi = "10.1186/1471-2350-14-113",

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T1 - Studies of association of AGPAT6 variants with type 2 diabetes and related metabolic phenotypes in 12,068 Danes

AU - Snogdal, Lena Sønder

AU - Grarup, Niels

AU - Banasik, Karina

AU - Wod, Mette

AU - Jørgensen, Torben

AU - Witte, Daniel R

AU - Lauritzen, Torsten

AU - Nielsen, Aneta Aleksandra

AU - Brandslund, Ivan

AU - Christensen, Cramer

AU - Pedersen, Oluf

AU - Yderstræde, Knud Bonnet

AU - Beck-Nielsen, Henning

AU - Henriksen, Jan Erik

AU - Hansen, Torben

AU - Højlund, Kurt

PY - 2013/10/25

Y1 - 2013/10/25

N2 - 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.

AB - 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.

U2 - 10.1186/1471-2350-14-113

DO - 10.1186/1471-2350-14-113

M3 - Journal article

C2 - 24156295

SN - 1471-2350

VL - 14

SP - 113

JO - BMC Medical Genetics

JF - BMC Medical Genetics

IS - 1

ER -

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

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