ABSTRACT
Purpose: Calcineurin inhibitors (CNIs) such as tacrolimus are a major immunosuppressive therapy after renal transplantation, which inhibit cytokine expression. The pharmacokinetics of such drugs is influenced by cytochrome P450 (CYP) enzymes, multi-drug resistance-1 (MDR-1), and C25385T pregnane X receptor (PXR). This study aimed to investigate the impact of single nucleotide polymorphisms (SNP) in these genes on the ratio of tacrolimus level per drug dosage (C/D ratio), acute graft rejection, and viral infections. Methods: Kidney transplantation recipients (n=65) under similar immunosuppressive treatment were included. Amplification refractory mutation systempolymerase chain reaction (ARMS-PCR) method was applied to amplify the loci containing the SNPs of interest. Results: Overall, 65 patients with a male/female ratio of 37/28 were included. The mean age was 38±1.75 years. The variant allele frequencies of CYP3A5*3, MDR-1 C3435T, and PXR C25385T were 95.38, 20.77, and 26.92%, respectively. No significant correlations were found between the studied SNPs and the tacrolimus C/D ratios. However, there was a significant difference in the C/D ratios at 2 and 8 weeks in homozygote CYP3A5 *3/*3 carriers (P=0.015). No significant association was found between the studied polymorphisms and viral infections and acute graft rejection (P>0.05). Conclusion: Homozygote CYP3A5 *3/*3 genotype could influence the tacrolimus metabolism rate (C/D ratio).
ABSTRACT
INTRODUCTION: Organ donation is one of the surviving procedures, which can increase the life expectancy of end-stage patients. Inappropriate beliefs and attitude of individuals to organ donation, their poor knowledge, and the socio-economic level are one of the most important barriers for organ donation. Therefore, here knowledge and attitude levels among relatives of trauma patients regarding organ donation were evaluated. METHODS: This cross-sectional study was done on relatives of trauma patients referred to the emergency department of Sina Hospital, Tabriz, Iran, through 2013 to 2014. The questionnaire included parts of demographic data and socio-economic situations as well as status of knowledge and attitude regarding organ donation. A score between 0-7 was belonged to each person based on his/her level of knowledge. Attitude level had a score between 0-12. Chi- square, Fisher, and Mann-Whitney U test were performed to assess the relation between demographic variables and the level of knowledge and attitude. P<0.05 was considered as a significant level. RESULTS: 79 persons (57.1% male) with the mean age of 31.3±11.3 years were evaluated. 57 (73.1%) of subjects agreed with organ transplant. The main causes of disagreement among relatives regarding organ donation were dissatisfaction of the donor's relatives (25%) and religious issues (15%). 49 (62.02%) studied people had inappropriate attitude and 27 (34.2%) ones had good knowledge. male gender (OR=5.87; 95%CI: 3.32-8.42; p=0.001) and self-employed job (OR=7.78; 95%CI: 4.64-10.92; p=0.001) are independent factors associated with poor knowledge about organ donation. Self-employed job (OR=3.86; 95%CI: 1.41-6.11; p=0.009) and poor knowledge (OR=15.3; 95%CI: 9.03-21.57; p<0.001) were related to inappropriate attitude toward organ donation. CONCLUSION: The present study showed that 73.1% of participants agreed with organ donation. The major causes of disagreements were dissatisfaction of other relatives and religious beliefs. 62.0% of the studied people had positive view regarding organ donation and 34.2% of them well informed about. The most important causative factors for poor knowledge in this context were male gender and self-employed occupation. In addition, poor knowledge and self-employed job were two factors associated with inappropriate attitude toward organ donation.
