Investigation of the 1846G>A variation of CYP2D6 gene in a Randomly Selected Sample of Syrian population

Abstract

Background and aim: Individuals' response to drugs varies as a result of a number of factors, differences in genetic makeup is considered as the most important one. This highlights the importance of personalized medicine based on genetic variations. Cytochrome enzymes play an essential role in drug metabolism and the CYP2D6 enzyme is considered a pivotal player in this process. It is responsible for metabolizing 20% of commonly used drugs, and is responsible for bioactive activation of a number of primary drugs and converting them to an effective form such as converting codeine to morphine inside the body that relieves pain. Some genetic variations in the CYP2D6 gene modify the enzyme's activity leading to not achieving the therapeutic target ,  appearance of side effects and toxicity . Our research aims to investigate the frequency of the 1846G > A variation specific to the non-functional CYP2D6 * 4 in a randomly selected sample of Syrian society

Materials and methods: 50 Syrians participants were recruited in the study and the 1846G > A variation was detected using PCR-RFIP method.

Results: the presence of AA, GA, GG genotypes were 4%, 48%, 48%, respectively, and the frequency of allele G was 72% and allele A was 28%. The statistical study showed that allele A enhances the appearance of side effects among participants.

Conclusion: Determining the genetic composition of individuals is a very important process as it helps health care workers select the appropriate therapeutic protocol for each individual. Our study has shown a marked frequency of the 1846G > A variation in the sample studied. This reinforces the need to investigate further genetic changes within the CYP2D6 and other cytochrome genes that are highly relevant to drug metabolism.