A Key GWAS-Identified Genetic Variant Contributes to Hyperlipidemia by Upregulating miR-320a.

ABSTRACT: It has been unclear whether the elevated levels of the circulating miR-320a in patients with coronary artery disease is due to environmental influence or genetic basis. By recombinant adeno-associated virus (rAAV)-mediated loss- and gain-of-function studies in the mouse liver, we revealed that elevated miR-320a is sufficient to aggravate diet-induced hyperlipidemia and hepatic steatosis. Then, we analyzed the data from published genome-wide association studies and identified the rs12541335 associated with hyperlipidemia. We demonstrated that the rs13282783 T allele indeed obligated the silencer activity by preventing the repressor ZFP161 and co-repressor HDAC2 from binding to DNA that led to miR-320a upregulation. We further confirmed this genetic connection on an independent population an

SUBMITTER: Yin Z 

PROVIDER: S-EPMC7689551 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature