Fine Mapping and Functional Analysis Reveal a Role of SLC22A1 in Acylcarnitine Transport.

ABSTRACT: Genome-wide association studies have identified a signal at the SLC22A1 locus for serum acylcarnitines, intermediate metabolites of mitochondrial oxidation whose plasma levels associate with metabolic diseases. Here, we refined the association signal, performed conditional analyses, and examined the linkage structure to find coding variants of SLC22A1 that mediate independent association signals at the locus. We also employed allele-specific expression analysis to find potential regulatory variants of SLC22A1 and demonstrated the effect of one variant on the splicing of SLC22A1. SLC22A1 encodes a hepatic plasma membrane transporter whose role in acylcarnitine physiology has not been described. By targeted metabolomics and isotope tracing experiments in loss- and gain-of-function cell and m

SUBMITTER: Kim HI 

PROVIDER: S-EPMC5630162 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature