Variants in the PPARγ gene affect fatty acid and glycerol metabolism in familial combined hyperlipidemia

• Published in: Molecular genetics and metabolism 2003-11, Vol.80 (3), p.296-301
• Main Authors: Eurlings, Petra M.H, van der Kallen, Carla J.H, Vermeulen, Vicky M.M.-J, de Bruin, Tjerk W.A
• Format: Article
• Language: English
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/S1096-7192(03)00138-0

Familial combined hyperlipidemia (FCHL) is a common genetic lipid disorder characterized by premature coronary artery disease, dyslipidemia, insulin resistance, and impaired adipose tissue free fatty acid (FFA) metabolism. Increased adipose tissue FFA flux towards the liver may, in part, contribute to reduced insulin sensitivity and hyperlipidemia in FCHL. It was the objective of the present study to evaluate the contribution of the peroxisome proliferator-activated receptor γ (PPARγ) gene to FCHL traits related to adipocyte lipid metabolism, dyslipidemia, and insulin resistance. In a case-control panel consisting of 79 FCHL probands and 124 spouse controls, polymorphic marker D3S1259 and three intragenic PPARγ variants, i.e., 161C > T, Pro12Ala, and Pro115Gln, were studied. The Pro115Gln variant was not found in any of the subjects. Allele frequencies of the 161C > T, Pro12Ala variants, and D3S1259 did not differ significantly between FCHL probands and spouses. In FCHL probands, individuals heterozygous or homozygous for the 161T allele had lower plasma concentrations of FFA ( P