Ppar gene

The PPAR gene located on chromosome 3 p25.2 codes for a member of the peroxisome proliferator activated receptor (PPAR) subfamily. PPARs form heterodimers with retinoid X receptors (RXRs). These heterodimers regulate the transcription of various genes. There are 3 known subtypes of PPARs: PPARα, PPARß and PPARƴ.

PPARƴist is a receptor protein which belongs together with PPARα [NR1C1] and PPARß [NR1C2] to the superfamily of cytosolic steroid receptors. PPARƴ acts as a ligand-activated transcription factor and is ubiquitously expressed. Both saturated and unsaturated fatty acids, eicosanoids and prostaglandins have been identified as natural ligands of the encoded protein.

Mutations and polymorphisms of the PPAR gamma protein are known to be associated with various diseases:

• Carotide intimal medial thickness 1 OMIM: 609338 (Wang X L et al. 1999)
• Insulin resistance, severe, digenic OMIM: 604367 (Savage DB et al. 2002)
• Partial familial lipodystrophy type 3 OIMI:604367 (Ludtke A et al. 2007)
• Obesity, severe OMIM: 601665
• Colon carcinoma OMIM:164790

1. Deeb S et al (1998) A pro12ala substitution in PPAR-gamma-2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nature Genet 20: 284-287
2. Fajas L et al (2002) The retinoblastoma-histone deacetylase 3 complex inhibits PPAR-gamma and adipocyte differentiation. Dev. cell 3: 903-910
3. Fajas L et al (2002) E2Fs regulate adipocyte differentiation. Dev. cell 3: 39-49.
4. Ludtke A et al (2007) Peroxisomes proliferator-activated receptor-gamma C190S mutation causes partial lipodystrophy. J. Clin. Endocr. Metab. 92: 2248-2255
5. Mukherjee R et al (1997) Identification, characterization, and tissue distribution of human peroxisome proliferator-activated receptor (PPAR) isoforms PPAR-gamma-2 versus PPAR-gamma-1 and activation with retinoid X receptor agonists and antagonists. J Biol Chem 272: 8071-8076
6. Sarraf Pet al (1999) Loss-of-function mutations in PPAR-gamma associated with human colon cancer. Molec. Cell 3: 799-804.
7. Savage DB et al (2002) Digenic inheritance of severe insulin resistance in a human pedigree. Nature Genet. 31: 379-384
8. Wang X L et al (1999) Peroxisomes proliferator-activated receptor gamma C161-T polymorphism and coronary artery disease. Cardiovasc. Res. 44: 588-594