The non-functional polymorphism in CYP2D6 gene (CYP2D6*4): Report of frequency and assessment of CYP2D6*4 association with response to atorvastatin, in patients with high LDL level in North of Iran, Guilan Province

Background: Individuals respond to statins differently due to genetic variations. One of the most significant enzymes involved in drug metabolism is CYP2D6 enzyme, coded by the CYP2D6 gene. Individuals who carry two non-functional alleles in this gene are considered as poor metabolizers (PMs). Recognizing poor metabolizers might help in preventing adverse effects of drugs. Objective: In this study, the association between CYP2D6*4, the most frequent non-functional allele, and atorvastatin response was assessed for the first time in Iranian individuals. Material and Method: A total of 180 individuals suffering from high LDL level took atorvastatin for 8 weeks to assess their response. The patients were genotyped for CYP2D6*4 polymorphism, using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method and the results were validated by sanger sequencing. The association between CYP2D6*4 allele and atorvastatin response was assessed. Results: In this population, the allele frequency of the CYP2D6*4 variant was 7%. This allele was not observed in the homozygote state in the current study. There was no statistically significant association between this polymorphism and atorvastatin response.  Observed allelic frequency was close to the previous findings in Iranian healthy individuals. Lack of association might be a result of CYP2D6*4 low frequency in this population. Conclusion: The CYP2D6*4 variant probably is not related to poor metabolizers in the North of Iran, especially to poor metabolizers of atorvastatin. Therefore, to distinguish poor metabolizers in this region, further investigations on other genes are recommended.