A Comparative Study to illustrate the Effects of Beta-1 Adrenergic Receptor Allelic Polymorphism on Disease Outcome in Iraqi Patients with Acute Coronary Syndrome (on Metoprolol Therapy)
Objective: The response to metoprolol therapy in patients with acute coronary syndrome (ACS) is variable and a substantial element of this variability is linked to variation in CYP2D6 enzyme and adrenoreceptor (ADRB1) alleles, genotype polymorphism, affecting the phenotype in terms of both rate of metabolism of the active metoprolol (and hence its metabolic ratio) and the responsiveness of ADRB1 receptors to bound metoprolol. This study aims to investigate different clinically relevant allele variants (allele frequencies) of ADRB1 genes: (Arg389Gly: Gly/Gly, Gly/Arg, Arg/Gly) and to determine whether a specific genotype of Beta-1 adrenergic receptor genes (based on genetic polymorphism "allelic types" and combination) have impact on metoprolol effectiveness (clinical outcome) in Arabic Iraqi patients with ACS. Methods: Two-hundred and fifty patients with ACS were enrolled in this study and divided into 2 study groups: Group 1 (125 ACS patients receiving metoprolol) and Group 2 (125 ACS patients received no metoprolol therapy). Two millilitres of venous blood samples were collected and stored at -20 C for DNA extraction. Urine samples were also collected to assess the metabolic ratio using High-performance liquid chromatography (HPLC). Results: There were significant variations in the distribution of the Iraqi patients with respect to CYP2D6 allelic polymorphism in comparison with nearby, Western and Eastern countries and that significant difference contributed to patients’ outcome in terms of morbidity and mortality in respect to variable genotypes and phenotypes. Conclusion: These findings suggest that individualization of metoprolol in patients with ACS is essential to improve patients’ outcome.