Impact of a variable number tandem repeat in the CYP2C9 promoter on warfarin sensitivity and responsiveness in Jordanians with cardiovascular disease.

Abstract

PurposeThe purpose of this study was to investigate the influence of CYP/CYP450 2C9 (CYP2C9) promoter variable number tandem repeat (p-VNTR) polymorphism on susceptibility to cardiovascular disease and on warfarin sensitivity and responsiveness, in Jordanians with cardiovascular disease during initiation and stabilization phases of therapy.Patients and methodsA total of 211 cardiovascular patients who were being treated with warfarin anticoagulants and 205 healthy individuals were enrolled in this study. PCR-based methods were performed to analyze the effects of CYP2C9 p-VNTR polymorphism on warfarin metabolism. The p-VNTR polymorphism was composed of tandem repeat motifs sorted into three alleles based on the length and structure: short (p-VNTR-S), middle (p-VNTR-M), and long (p-VNTR-L).ResultsWe found that the genotypic and allelic frequencies differ significantly between patients and healthy individuals; therefore, our results suggest that this polymorphism is associated with cardiovascular disease in the Jordanian population. Moreover, during the initiation phase of therapy, 20% of warfarin-sensitive patients were homozygous for a short allele (p-VNTR-S), and 12.2% were heterozygous for this allele (p-VNTR-M/p-VNTR-S). During the stabilization phase, no significant differences were found between these groups and their genotypic frequencies. Additionally, we did not confirm any relationship between the CYP2C9 p-VNTR polymorphism and warfarin response during either the initiation or the stabilization phases of therapy.ConclusionOur data show a significant difference between the CYP2C9 p-VNTR polymorphism and risk of cardiovascular disease, in addition to significant association between this polymorphism and sensitivity to warfarin at the initiation phase of therapy in a Jordanian population. However, there is no correlation between this polymorphism and warfarin response, international normalized ratio (INR) values, or required warfarin dose to achieve a target INR either at the initiation or stabilization phases of therapy. To further corroborate our results, additional studies are required with a larger number of samples and different ethnic groups.