Allelic Frequency of Single-Nucleotide Polymorphisms in CYP2C9, VKORC1, and CYP4F2 Genetic Variants in Patients With Mechanical Heart Valves on Acenocoumarol Drug Therapy.

Background Patients with mechanical heart valves require lifelong anticoagulation with vitamin K antagonists (VKAs), such as acenocoumarol. However, acenocoumarol has a narrow therapeutic index, and genetic variants in CYP2C9, VKORC1, and CYP4F2 significantly influence individual dose requirements and the risk of adverse events. Limited data exist on the prevalence of these clinically important variants in Central Indian populations. Objectives To determine the frequency of clinically significant genetic variants, alleles, and metabolizer phenotypes of the CYP2C9, VKORC1, and CYP4F2 genes, and to evaluate their clinical relevance in patients undergoing mechanical heart valve replacement with acenocoumarol anticoagulant therapy. Methods A total of 100 adults diagnosed with valvular heart disease with mechanical heart valve replacement and receiving acenocoumarol were enrolled from the cardiothoracic surgery department of All India Institute of Medical Sciences (AIIMS) Bhopal, India. Genotyping for CYP2C9*2, CYP2C9*3, VKORC1 c.-1639G>A, and CYP4F2 V433M variants was performed using TaqMan quantitative real-time polymerase chain reaction (qPCR). Ethical approval was obtained from the institutional human ethics committee, and written informed consent was obtained from all participants. Results Among the participants, 53% underwent mitral valve replacement, 31% underwent aortic valve replacement, and 16% underwent double-valve replacement. Rheumatic heart disease was the underlying cause in 95% of patients. Ischemic heart disease was the most common comorbidity. For CYP2C9*2, the major, minor, and heterozygous allele frequencies were 91%, 4%, and 5%, respectively. For CYP2C9*3, these were 86%, 9%, and 5%; for VKORC1, 68%, 3%, and 29%; and for CYP4F2, 60%, 8%, and 32%, respectively. The frequencies of normal, intermediate, poor, and rapid metabolizers were 36%, 44%, 15%, and 5%, respectively. Conclusions The study demonstrates a high prevalence (64%) of actionable CYP2C9, VKORC1, and CYP4F2 genotypes among the study participants. Genotype-guided dosing of acenocoumarol can potentially improve treatment outcomes and minimize adverse events in patients with valvular heart disease and mechanical valve replacement.