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.

PurposeThis study aims to investigate the relationships between genetic polymorphisms of the coagulation factor VII (FVII) gene and warfarin responsiveness and sensitivity.Patients and methodsThe study population consisted of 417 subjects (207 Jordanian cardiovascular patients and 210 healthy individuals). Cardiovascular patients were classified into two groups: those sensitive to warfarin dosage (sensitive, moderate, and resistant) and those responsive to warfarin based on International Normalized Ratios (INRs; poor, good, and extensive responders). The HVR4 polymorphism of the FVII gene was genotyped.ResultsOur results showed that there are significant differences between patients and controls according to both genotypic and allelic frequencies (P<0.0001) in the genetic susceptibility study. Moreover, the pharmacogenetics study reported that HVR4 had no association with warfarin sensitivity or responsiveness during the initiation and maintenance phases of therapy, the only significant differences were in the INR outcome measured during the maintenance phase of therapy (P=0.012).ConclusionOur data suggests lacking of association between the HVR4 polymorphism in the FVII gene and warfarin sensitivity and responsiveness during the initiation and maintenance phases of therapy. It is possible that these patients carry additional mutations in genes involved in the coagulation pathway.

Background/aim: The ERBB4 gene encodes a transmembrane tyrosine kinase and is considered to be one of the risk genes of schizophrenia. Although there is evidence of the roles of genes and the environment in the etiology of schizophrenia, a comprehensive biological and genetic background of the disease is still lacking. The aim of this study is to assess whether genetic variation in the human ERBB4 gene is associated with vulnerability to schizophrenia in the Jordanian Arab population. Materials and methods:A total of 185 inpatients with schizophrenia participated in this study and 195 healthy genetically homogeneous individuals were also used as controls. Two genetic variants, rs839523 (G/A, intron 2) and rs3748962 (A/G, exon 27), encompassing the ERBB4 gene were genotyped using DNA sequencing. Results:The results revealed a strong and statistically significant genetic association of rs839523 with schizophrenia (P = 0.002 for allele and P = 0.006 for genotype). Conclusion:This study provides strong statistical evidence that there is an association between the ERBB4 gene and schizophrenia in a Jordanian population of Arab descent.