The L162V Polymorphism of the Peroxisome Proliferator Activated Receptor Alpha Gene (PPARA) is not Associated with Type 2 Diabetes, BMI or Body Fat Composition

Abstract

The L162V single nucleotide polymorphism in PPARA is suggested to play an important role in the pathogenesis of type 2 diabetes, obesity, and body fat composition. However, clinical evidence is controversial. Our aim was to investigate the relationships of the L162V SNP with type 2 diabetes, pre-diabetes phenotypes, adiposity, and plasma lipid levels. In addition, we studied the associations of the L162V SNP with body fat composition, intramyocellular lipids, and liver fat content. Furthermore, we examined if the L162V SNP was associated with changes in BMI, insulin secretion, insulin resistance, body fat composition, intramyocellular lipids, and liver fat content in response to lifestyle intervention. Data from two large cross sectional studies, the combined TULIP/TUEF cohorts, and the LURIC study were analysed. Prospective data were obtained from TULIP participants who underwent a lifestyle intervention. A total of 4,779 subjects were studied. BMI was measured in all subjects. Type 2 diabetes was diagnosed in a subgroup of the LURIC study. In the TULIP study total body fat, non-visceral adipose tissue, and visceral adipose tissue were measured with magnetic resonance tomography. Liver fat and intramyocellular lipid content were quantified with (1)H magnetic resonance spectroscopy. Insulin sensitivity and insulin secretion were estimated from oral glucose tolerance testing. The L162V SNP was neither associated with type 2 diabetes or BMI nor with body fat composition, intramyocellular lipids or liver fat content. According to our study, the L162V SNP does not have a strong impact on the pathogenesis of type 2 diabetes or obesity.