Candidate Genes for Prediction of Efficacy and Safety of Statin Therapy in the Kazakh Population

Abstract

The purpose of this research was to determine the frequency of mutation of the cytochrome CYP3A5 genes and transport proteins SLCO1B1 and MDR1 in patients with coronary heart disease in the Kazakh nation. A prospective cohort clinical and genetic study was conducted. The study was conducted in 2017−2019. Medical records containing information about drug prescription conducted in hospitals and outpatient departments were carefully analyzed. In the examined group of 178 patients treated with statins, a significant frequency of genetic variants that determine the increased risk of complications of statin use was revealed. There was a tendency toward an increase in the activity of creatine phosphokinase (CPK) in the blood upon detection of the A6986G mutation of the cytochrome gene and SLCO1B1 (c.521T>C) gene of the transport protein OATP1B1. In the studied Kazakh population, the presence of a homozygous mutant SLCO1B1 gene of the transport protein can be recommended as a genetic marker for the undesirability of using antihypercholesterolemic therapy with statins, which simultaneously leads to a decrease in the effectiveness of treatment and an increase in the risk of side effects.

Statin-Associated Liver Dysfunction and Muscle Injury: epidemiology, Mechanisms, and Management Strategies

“…However, the issues of ADR-related drug safety of statins have also aroused great concerns. 8 ADR not only causes additional harm to patients, but also greatly interferes with clinical routine treatment. It is necessary to put on the agenda to systematically manage the use of statins in clinical practice.…”