Peroxisome proliferator-activated receptor-delta genotype influences metabolic phenotype and may influence lipid response to statin therapy in humans: a genetics of diabetes audit and research Tayside study

J Clin Endocrinol Metab. 2010 Apr;95(4):1830-7. doi: 10.1210/jc.2009-1201. Epub 2010 Mar 3.

Abstract

Context: Previous studies have identified a single-nucleotide polymorphism in the gene encoding peroxisome proliferator-activated receptor-delta (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 TNFalpha and was dependent on gender.

Conclusion: The current results suggest differential effects of PPARdelta in males and females.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / blood
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Body Mass Index
  • Cholesterol / blood
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Gene Frequency
  • Genotype
  • Haplotypes
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hyperlipidemias / drug therapy*
  • Hyperlipidemias / genetics*
  • Leptin / blood
  • Lipids / blood*
  • Male
  • Middle Aged
  • PPAR delta / genetics*
  • PPAR delta / metabolism*
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sex Characteristics
  • Tumor Necrosis Factor-alpha / blood
  • Young Adult

Substances

  • Adiponectin
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Leptin
  • Lipids
  • PPAR delta
  • Tumor Necrosis Factor-alpha
  • Cholesterol