Peroxisome Proliferator-Activated Receptor-δ Genotype Influences Metabolic Phenotype and May Influence Lipid Response to Statin Therapy in Humans: A Genetics of Diabetes Audit and Research Tayside Study

Context: Previous studies have identified a single-nucleotide polymorphism in the gene encoding peroxisome proliferator-activated receptor-δ (PPARD), rs2016520, that is associated with changes in metabolic disease in some but not all studies, which suggests that PPARD agonists may have therapeutic benefits for the treatment of metabolic disorders, including dyslipidemia, type 2 diabetes, and obesity. Objective: The objective of the study was to determine whether rs2016520 or other single-nucleotide polymorphism in the PPARD locus influenced the risk of developing various characteristics of metabolic disease. Design: Haplotype tagging analysis across PPARD was performed in 11,074 individuals from the Welcome Trust U.K. Type 2 Diabetes Case Control Collection. Results: In subjects with and without type 2 diabetes, rs2016520 was associated with body mass index, high-density lipoprotein cholesterol, leptin, and TNFα and was dependent on gender. Conclusion: The current results suggest differential effects of PPARδ in males and females. PPARδ is associated with traits that influence the risk of developing metabolic disease; this risk association is dependant upon gender.