Genetic variation in statin intolerance and a possible protective role for UGT1A1

• Published in: Pharmacogenomics Vol. 19; no. 2; pp. 83 - 94
• Main Authors: V Willrich, Maria Alice, Kaleta, Erin J, Bryant, Sandra C, Spears, Grant M, Train, Laura J, Peterson, Sandra E, Lennon, Vanda A, Kopecky, Stephen L, Baudhuin, Linnea M
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.01.2018
• Subjects: ABC transporters; Cardiology; Cardiovascular disease; Clinical medicine; Consortia; Creatine; Creatine kinase; Drug dosages; Enzymes; Etiology; Gene frequency; Genetic analysis; Genetic diversity; Intolerance; Lipids; Liver; Metabolism; Muscle pain; Statins; Toxicity; genetic variants; myotoxicity; CYP3A; GATM; UGT; statins; SLC transporters; precision medicine; ABC transporters; statin intolerance
• ISSN: 1462-2416; 1744-8042
• DOI: 10.2217/pgs-2017-0146

The etiology of statin intolerance is hypothesized to be due to genetic variants that impact statin disposition and clearance. We sought to determine whether genetic variants were associated to statin intolerance. The studied cohort consisted of hyperlipidemic participants (n = 90) clinically diagnosed with statin intolerance by a cardiologist and matched controls without statin intolerance. Creatine kinase activity, lipid profiles and genetic analyses were performed on genes involved in statin metabolism and included UGT1A1 and UGT1A3 sequencing and targeted analyses of CYP3A4*22, CYP3A5*3, SLCO1B1*5 and *1b, ABCB1 c.3435C>T, ABCG2 c.421C>A and GATM rs9806699. Although lipids were higher in cases, genetic variant minor allele frequencies were similar between cases and controls, except for UGT1A1*28, which was less prevalent in cases than controls.