AUTHOR=Chai Tianci , Wang Zhisheng , Yang Xiaojie , Qiu Zhihuang , Chen Liangwan 

TITLE=PSRC1 May Affect Coronary Artery Disease Risk by Altering CELSR2, PSRC1, and SORT1 Gene Expression and Circulating Granulin and Apolipoprotein B Protein Levels

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.763015

DOI=10.3389/fcvm.2022.763015

ISSN=2297-055X

ABSTRACT=<sec><title>Objective</title><p>The aim of the study was to identify additional factors that contributed to coronary artery disease (CAD).</p></sec><sec><title>Methods</title><p>We conducted integrative analysis on publicly available data from genome-wide association studies and quantitative trait locus studies by employing Mendelian randomization methods to examine the associations of gene expression in liver cells and circulating protein levels with LDL-C and CAD.</p></sec><sec><title>Results</title><p>We found that the mRNA expression levels of <italic>CELSR2, PSRC1, SORT1, SYPL2, RHD, RHCE, ANGPTL3, ATXN7L2, DNAH11, FADS3, ST3GAL4, NYNRIN, CETP, EFCAB13</italic>, and <italic>SPTLC3</italic> were significantly associated with LDL-C. The expression levels of <italic>SORT1, PSRC1</italic>, and <italic>CELSR2</italic> in liver cells were significantly associated with CAD. Higher expression levels of <italic>SORT1, PSRC1</italic>, and <italic>CELSR2</italic> in the liver were significantly associated with lower circulating LDL-C levels and CAD risk. <italic>PSRC1</italic> variants were strongly associated with <italic>SORT1, PSRC1</italic>, and <italic>CELSR2</italic> gene expression in liver cells. Higher circulating granulin and apolipoprotein B levels, which were strongly affected by <italic>PSRC1</italic> variants, were significantly associated with higher LDL-C levels and CAD risk, with odds ratios of 1.15 (1.10–1.19) and 1.45 (1.21–1.74), respectively.</p></sec><sec><title>Conclusion</title><p>This study showed that regulatory SNPs in <italic>PSRC1</italic> may affect CAD risk by altering <italic>CELSR2, PSRC1</italic>, and <italic>SORT1</italic> gene expression in liver cells and circulating granulins and apolipoprotein B proteins.</p></sec>