Association of CYP2D6*4 Polymorphism With Response to Atorvastatin in Patients With High Low-Density Lipoprotein Level in Northern Iran, Guilan Provice

Abstract

Background: People who take statins respond differently to them due to genetic differences. One of the most significant enzymes involved in drug metabolism is cytochrome P450 2D6 (CYP2D6) enzyme, coded by the CYP2D6 gene. Individuals who carry two non-functional alleles in this gene are considered as poor metabolizers. Recognizing poor metabolizers may help prevent adverse effects of drugs. Objective: This study aims to assess the association of CYP2D6*4, as the most frequent non-functional allele of CYP2D6 gene, and response to atorvastatin in patients with high low-density lipoprotein (LDL) level in northern Iran. Methods: A total of 180 patients with high LDL level underwent treatment with atorvastatin for 8 weeks to assess their response. They were assessed in terms of CYP2D6*4 polymorphism using the amplification-refractory mutation system/polymerase chain reaction method and the results were validated by the sanger sequencing method. At the end, the association between CYP2D6*4 allele and response to atorvastatin was assessed. Results: In patients, the percentage of the CYP2D6*4 variant was 7%. This allele was not observed in homozygous patients. There was no significant association between CYP2D6*4 polymorphism and response to atorvastatin, which might be due to low frequency of CYP2D6*4 in patients. The observed allelic frequency was close to the frequency reported in previous studies for healthy Iranian people. Conclusion: It seems that CYP2D6*4 polymorphism is not the cause of poor metabolism in poor metabolizers in northern Iran. Therefore, to diagnose poor metabolizers in this region, further studies on other genes are recommended.