title: Single gene contributions: genetic variants of peroxisome proliferator-activated receptor (isoforms alpha, beta/delta and gamma) and mechanisms of dyslipidemias.
abstract: OBJECTIVE
  Polymorphisms in peroxisome proliferator-activated receptor isoforms may be among the most important single-gene contributors to dyslipidemias, insulin resistance, and maturity-onset diabetes.
  
  
  RESULTS
  Familial partial lipodystrophy is a rare but characteristic phenotype associated with carriers of peroxisome proliferator-activated receptor-gamma missense mutations. Mutant receptors are transcriptionally defective, exhibit aberrant affinity for co-regulator molecules, and can exert dominant-negative or haplo-insufficiency effects on normal peroxisome proliferator-activated receptor-gamma function. The P12A variant of isoform gamma is estimated to reduce diabetes risk by 19% in many populations, and has a large attributable risk because of high prevalence of the normal allele. Variants L162V and V227A of isoform alpha (common in white and Oriental populations, respectively) are associated with sexually dimorphic perturbations of lipid metabolism and cardiovascular risk. Polymorphisms in isoforms alpha and beta/delta are reported to influence lipid and glucose utilization. Apart from lipodystrophic syndromes, metabolic and cardiovascular risk in peroxisome proliferator-activated receptor variants is apparently modulated by dietary and exercise interventions, and interactions with polymorphisms in other genetic loci.
  
  
  CONCLUSIONS
  Polymorphisms in peroxisome proliferator-activated receptors are critical susceptibility risk factors for dyslipidemias and diabetes. They provide attractive targets for gene-environment interventions to reduce the burden of metabolic disease.
authors.affiliation: Department of Obstetrics & Gynecology, National University Hospital, Yong Loo Lin School of Medicine, National University of Singapore. obgyel@nus.edu.sg
authors.forename: Eu Leong
authors.initials: EL
authors.lastname: Yong
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Mei Hui
authors.initials: MH
authors.lastname: Liu
mesh_terms: D050171:Dyslipidemias / Q000235:genetics* / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D009154:Mutation / Q000235:genetics; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
chemical_list: D047492:Peroxisome Proliferator-Activated Receptors; D020033:Protein Isoforms