| First Author | Soccio RE | Year | 2015 |
| Journal | Cell | Volume | 162 |
| Issue | 1 | Pages | 33-44 |
| PubMed ID | 26140591 | Mgi Jnum | J:356475 |
| Mgi Id | MGI:7762567 | Doi | 10.1016/j.cell.2015.06.025 |
| Citation | Soccio RE, et al. (2015) Genetic Variation Determines PPARgamma Function and Anti-diabetic Drug Response In Vivo. Cell 162(1):33-44 |
| abstractText | SNPs affecting disease risk often reside in non-coding genomic regions. Here, we show that SNPs are highly enriched at mouse strain-selective adipose tissue binding sites for PPARgamma, a nuclear receptor for anti-diabetic drugs. Many such SNPs alter binding motifs for PPARgamma or cooperating factors and functionally regulate nearby genes whose expression is strain selective and imbalanced in heterozygous F1 mice. Moreover, genetically determined binding of PPARgamma accounts for mouse strain-specific transcriptional effects of TZD drugs, providing proof of concept for personalized medicine related to nuclear receptor genomic occupancy. In human fat, motif-altering SNPs cause differential PPARgamma binding, provide a molecular mechanism for some expression quantitative trait loci, and are risk factors for dysmetabolic traits in genome-wide association studies. One PPARgamma motif-altering SNP is associated with HDL levels and other metabolic syndrome parameters. Thus, natural genetic variation in PPARgamma genomic occupancy determines individual disease risk and drug response. |
