Interrogation of the Atherosclerosis-Associated SORT1 (Sortilin 1) Locus With Primary Human Hepatocytes, Induced Pluripotent Stem Cell-Hepatocytes, and Locus-Humanized Mice.

ABSTRACT:

Objective

The noncoding single-nucleotide polymorphism rs12740374 has been hypothesized to be the causal variant responsible for liver-specific modulation of SORT1(sortilin 1) expression (ie, expression quantitative trait locus) and, by extension, the association of the SORT1 locus on human chromosome 1p13 with low-density lipoprotein cholesterol levels and coronary heart disease. The goals of this study were to compare 3 different hepatocyte models in demonstrating that the rs12740374 minor allele sequence is responsible for transcriptional activation of SORT1 expression.

Approach and results

We found that although primary human hepatocytes of varied rs12740374 genotypes strongly replicated the SORT1 expression quantitative trait locus observed p

SUBMITTER: Wang X 

PROVIDER: S-EPMC5746470 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature