Genetic Variation Determines PPARγ Function and Antidiabetic Drug Response In Vivo [ChIP-seq]

ABSTRACT: 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 PPARγ, a nuclear receptor for antidiabetic drugs. Many such SNPs alter binding motifs for PPARγ or cooperating factors, and functionally regulate nearby genes whose expression is strain-selective and imbalanced in heterozygous F1 mice. Moreover, genetically-determined binding of PPARγ 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 PPARγ binding, provide a molecular mechanism for some expression quantitative trait loci, and are risk factors fo

ORGANISM(S): Homo sapiens

SUBMITTER: Mitchell Lazar 

PROVIDER: E-GEOD-64458 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress