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.
authors.forename: Lena Sønder
authors.initials: LS
authors.lastname: Snogdal
authors.forename: Niels
authors.initials: N
authors.lastname: Grarup
authors.forename: Karina
authors.initials: K
authors.lastname: Banasik
authors.forename: Mette
authors.initials: M
authors.lastname: Wod
authors.forename: Torben
authors.initials: T
authors.lastname: Jørgensen
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Witte
authors.forename: Torsten
authors.initials: T
authors.lastname: Lauritzen
authors.forename: Aneta A
authors.initials: AA
authors.lastname: Nielsen
authors.forename: Ivan
authors.initials: I
authors.lastname: Brandslund
authors.forename: Cramer
authors.initials: C
authors.lastname: Christensen
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.forename: Knud
authors.initials: K
authors.lastname: Yderstræde
authors.forename: Henning
authors.initials: H
authors.lastname: Beck-Nielsen
authors.forename: Jan Erik
authors.initials: JE
authors.lastname: Henriksen
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.forename: Kurt
authors.initials: K
authors.lastname: Højlund
mesh_terms: D015992:Body Mass Index; D016022:Case-Control Studies; D003718:Denmark; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics; D015810:Linkage Disequilibrium; D008055:Lipids / Q000097:blood; D009765:Obesity / Q000235:genetics; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D055105:Waist Circumference
chemical_list: D007328:Insulin; D008055:Lipids; C529123:GPAT4 protein, human; D005992:Glycerol-3-Phosphate O-Acyltransferase