TY - JOUR
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 - B M C Medical Genetics
JF - B M C Medical Genetics
IS - 1
ER -
