RESUMEN
Drug metabolizing enzymes participate in the neutralizing of xenobiotics and biotransformation of drugs. Human cytochrome P450, particularly CYP1A1, CYP2C9, CYP2C19, CYP3A4 and CYP3A5, play an important role in drug metabolism. The genes encoding the CYP enzymes are polymorphic, and extensive data have shown that certain alleles confer reduced enzymatic function. The goal of this study was to determine the frequencies of important allelic variants of CYP1A1, CYP2C9, CYP2C19, CYP3A4 and CYP3A5 in the Jordanian population and compare them with the frequency in other ethnic groups. Genotyping of CYP1A1(m1 and m2), CYP2C9 (2 and 3), CYP2C19 (2 and 3), CYP3A4 5, CYP3A5 (3 and 6), was carried out on Jordanian subjects. Different variants allele were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). CYP1A1 allele frequencies in 290 subjects were 0.764 for CYP1A1 1, 0.165 for CYP1A1 2A and 0.071 for CYP1A1 2C. CYP2C9 allele frequencies in 263 subjects were 0.797 for CYP2C9 1, 0.135 for CYP2C9 2 and 0.068 for CYP2C9 3. For CYP2C19, the frequencies of the wild type (CYP2C19 1) and the nonfunctional (2 and 3) alleles were 0.877, 0.123 and 0, respectively. Five subjects (3.16 %) were homozygous for 2/2. Regarding CYP3A4 1B, only 12 subjects out of 173 subjects (6.9 %) were heterozygote with none were mutant for this polymorphism. With respect to CYP3A5, 229 were analyzed, frequencies of CYP3A5 1, 3 and 6 were 0.071, 0.925 and 0.0022, respectively. Comparing our data with that obtained in several Caucasian, African-American and Asian populations, Jordanians are most similar to Caucasians with regard to allelic frequencies of the tested variants of CYP1A1, CYP2C9, CYP2C19, CYP3A4 and CYP3A5.
Asunto(s)
Hidrocarburo de Aril Hidroxilasas/genética , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP3A/genética , Frecuencia de los Genes , Citocromo P-450 CYP2C19 , Citocromo P-450 CYP2C9 , Humanos , Jordania , Polimorfismo de Longitud del Fragmento de Restricción , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: Hypertension affects 70-90 % of all kidney transplant recipients. It is associated with poor graft survival and is a contributing factor to the increased cardiovascular mortality. The reasons for the insufficient blood pressure control in transplanted patients have not been thoroughly investigated. OBJECTIVE: To evaluate the extent of blood pressure control in Jordanian hypertensive renal transplant recipients and to assess factors associated with such control. SETTING: Three outpatient renal transplant clinics in Amman. METHOD: A cross-sectional observational study including 181 patients. We have considered blood pressure <130/80 mm Hg as controlled hypertension. Bivariate and multivariate logistic regression analyses were used to determine clinical factors associated with achievement of blood pressure control. MAIN OUTCOME MEASURES: Proportion of patients who achieved hypertension control and clinical factors associated with good blood pressure control. RESULTS: Mean systolic blood pressure was 128.6 ± 16.3 mm Hg and mean diastolic blood pressure was 82.8 ± 11.5 mm Hg. Blood pressure control was achieved only in 58 % of patients. The most commonly prescribed antihypertensives were calcium channel blockers (58 %) followed by beta-blockers (44 %). In bivariate analysis, female gender (p = 0.017) and creatinine clearance (p = 0.002) were positively associated, while number of antihypertensive medications was inversely associated (p = 0.04) with achievement of blood pressure control. After including these factors in multivariate logistic regression analysis, only creatinine clearance remained independently associated with hypertension control (odds ratio, OR 1.04; 95 % confidence interval [CI] 1.01-1.06; p = 0.003). CONCLUSION: Blood pressure control among renal transplant recipients in Jordan was found to be inadequate. The only factor found to be independently associated with adequate blood pressure control was creatinine clearance.