Publications (2)2.79 Total impact
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ABSTRACT: 1. The genetically polymorphic cytochrome P450 enzymes 2C9 (CYP2C9) and 2C19 (CYP2C19) are involved in the metabolism and elimination of a number of widely used drugs. The polymorphisms give rise to substantial interindividual and interethnic variability in drug excretion rates and final serum concentrations. For this reason, therapeutic responses and adverse drug reactions may vary from one person to another. In the present study we determined CYP2C9 and CYP2C19 genotypes in a random Iranian population to compare allele frequencies with previous findings in other ethnic groups. 2. Allelic variants of CYP2C9 (*1/*2/*3) and CYP2C19 (*1/*2/*3) were determined in 200 unrelated healthy Iranian volunteers by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays. 3. Fifteen subjects (7.5%) were homozygous for the CYP2C9*2 allele, whereas 21 individuals (10.5%) were heterozygous for this allele and 164 subjects (82%) had the wild-type allele (CYP2C9*1). No CYP2C9*3 was detected in the population sampled. Six subjects (3%) were homozygous for CYP2C19*2, whereas 44 individuals (22%) were heterozygous for this allele. In the remaining subjects (75%), no CYP2C19*2 was found. In addition, no CYP2C19*3 was detected in the population sampled. 4. Based on our data, the frequency of the CYP2C9*2 allelic variant in Iranians is similar to that in other Caucasian populations; however, the frequency of the CYP2C9*3 allele differed significantly (P < 0.05). Conversely, there was no difference in the frequency of CYP2C19 allelic variants between the present study and other studies evaluating this allele in Caucasian populations (P > 0.05).
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ABSTRACT: In addition to Human Leukocyte Antigens (HLA) compatibility, gene polymorphism in cytokines might be important in the quality of allogeneic immune response. OBJECTIVEs: In this study HLA-DR matching and a number of cytokine gene polymorphisms have been evaluated in occurrence of acute rejection after living-unrelated donor (LURD) kidney transplantation. A total of 42 renal transplants that were performed at Hashemi Nejad Kidney Hospital (Tehran/Iran) and then followed up for 3 months post-transplantation were included in our study. Using PCR-SSP, HLA-DR alleles (DR1-18) of recipient and donor pairs and gene polymorphisms in TNF-, TGF-1, IL-10, IL-6, and IFN- of recipients were determined. Acute rejection was observed in 11(26.2%) of 42 renal recipients. The frequency of one and two HLA-DR mismatches in rejector and nonrejector groups were 2(18.2%), 9(81.8%) and 13(41.9%), 17(54.8%) respectively. HLA-DR incompatibility was not significantly higher in rejector (1.820.40) than nonrejector (1.520.57) recipients (P=0.069) and more than half of nonrejectors had completely mismatched HLA-DR antigens with their donors. Polymorphisms associated with all the cytokines mentioned above were found to have no correlation with acute rejection. Regarding to high frequency of HLA-DR mismatching in nonrejector group, we can postulate that the immunogenecity of LURD renal transplant is not similar to the cadaveric one, and predictive value of HLA-DR mismatching for acute rejection is not as reliable as in cadaveric transplant. Although, there is no doubt about influence of HLA compatibility on allograft survival. In addition, we failed to demonstrate further association between combined recipient cytokine genotypes and HLA-DR matching with acute rejection in this study. Thus, we conclude that a more detailed immunogenetic profile is necessary to predict transplant outcome or immunosuppression tailoring.
Iran University of Medical ScienceTeheran, Tehrān, Iran