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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.

Studies of association of AGPAT6variants with type 2 diabetes and related metabolic phenotypes in 12,068 Danes