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BMC Med Genet. 2013 Oct 25;14:113. 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.

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.

PMID:
24156295
[PubMed - indexed for MEDLINE]
PMCID:
PMC4231429
Free PMC Article
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