AUTHOR=Dai Ruozhu , Zhao Xiaoyu , Zhuo Huilin , Wang Wei , Xu Yue , Hu Zixin , Zhang Tiexu , Zhao Jiangman 

TITLE=CYP2C19 metabolizer phenotypes may affect the efficacy of statins on lowering small dense low-density lipoprotein cholesterol of patients with coronary artery disease

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.1016126

DOI=10.3389/fcvm.2022.1016126

ISSN=2297-055X

ABSTRACT=<sec><title>Background</title><p>Dyslipidemia is a major cause of arteriosclerotic cardiovascular disease (ASCVD), and low-density lipoprotein cholesterol (LDL-C) is the profile to be reduced to prevent disease progression. Small dense low-density lipoprotein cholesterol (sdLDL-C) has been proven to be a more effective biomarker than LDL-C for ASCVD primary and secondary prevention. <italic>CYP2C19</italic> is an important drug metabolism gene. This study aimed to investigate the relationship between sdLDL-C and coronary artery disease (CAD) risk factors and explore the influence of <italic>CYP2C19</italic> metabolizer phenotypes on the sdLDL-C lowering efficacy of statins.</p></sec><sec><title>Methods</title><p>This study recruited 182 patients with CAD and 200 non-CAD controls. Baseline laboratory indices of fasting blood were detected, including blood lipids, glucose, and creatinine. In addition, LDL-C subfractions were separated and quantified. Gene polymorphisms of <italic>SLCO1B1</italic> and <italic>CYP2C19</italic> were detected in patients with CAD. The LDL-C subfractions levels of patients with CAD were followed up after statin drug treatment.</p></sec><sec><title>Results</title><p>Total cholesterol, LDL-C, LDLC-2, LDLC-3, LDLC-4, LDLC-5, LDLC-6, LDLC-7, and sdLDL-C levels of patients with CAD were significantly higher than those in non-CAD controls. Meanwhile, sdLDL-C (AUC = 0.838) and LDLC-4 (AUC = 0.835) performed outstandingly in distinguishing patients with CAD from controls. Based on <italic>CYP2C19</italic> metabolizer phenotypes, 113 patients with CAD were divided into the extensive metabolizer (EM, <italic>n</italic> = 49), intermediate metabolizer (IM, <italic>n</italic> = 52), and poor metabolizer (PM, <italic>n</italic> = 12) groups. The patients with IM and PM metabolizer phenotypes had better sdLDL-C lowering efficacy after taking statin drugs than patients with EM phenotype (<italic>P</italic> = 0.0268, FDR = 0.0536). The <italic>SLCO1B1</italic> genotype had no significant impact on the efficacy of statins (<italic>P</italic> = 0.1611, FDR = 0.1611).</p></sec><sec><title>Conclusion</title><p>sdLDL-C and LDLC-4 outperformed other blood lipids such as LDL-C for CAD risk screening. <italic>CYP2C19</italic> metabolizer phenotypes had the potential to predict the efficacy of statins in lowering sdLDL-C.</p></sec>