PPARG

HIGH

Peroxisome proliferator-activated receptor gamma

Chromosome: 3p25.2

Gene Overview

PPARG encodes a nuclear receptor that regulates adipocyte differentiation, lipid metabolism, and insulin sensitivity. The Pro12Ala variant (rs1801282) is associated with lower T2D risk and improved insulin sensitivity. PPARG is the target of thiazolidinediones (TZDs). It is central to metabolic and inflammatory pathways; diet and obesity strongly interact with genetic variation. Expression is highest in adipose tissue and macrophages.

Molecular Function

nuclear receptor activity
adipogenesis
insulin sensitivity

Protein class: nuclear receptor

Regulatory Annotation

Promoter activity: Ligand-activated; fatty acids and TZDs.

eQTL tissues: adipose tissue, macrophages

Tissue Expression Context

adipose tissueTPM range: 80-200GTEx vv8

Pathways

Linked Diseases & Exposures

Diseases

type-2-diabetes— GWAS; drug target, strength 0.88
obesity— pathway, strength 0.75

Exposures

diet-quality— literature, strength 0.8
obesity-exposure— literature, strength 0.78

Mechanistic Hypotheses

Pro12Ala reduces PPARγ activity; in the presence of high caloric intake, Ala carriers have lower T2D risk via improved insulin sensitivity.

GWAS; diet–gene interaction studies.

HIGH

Confidence Rating

Overall evidence confidence for this gene entry: HIGH

References

1.Grant SF, et al. (2006). PPARG and type 2 diabetes. Nature Genetics. doi:10.1038/ng1732