Elaheh Jabbari Hagh, Ali Mousavi, Seyyedeh Mina Hejazian, Mehdi Haghi, Samaneh Esfahanian, Elham Ahmadian, Sepideh Zununi Vahed, Mohammadreza Ardalan
{"title":"单核苷酸多态性对他克莫司在伊朗西北部肾移植受者体内药代动力学的影响。","authors":"Elaheh Jabbari Hagh, Ali Mousavi, Seyyedeh Mina Hejazian, Mehdi Haghi, Samaneh Esfahanian, Elham Ahmadian, Sepideh Zununi Vahed, Mohammadreza Ardalan","doi":"10.34172/apb.2023.038","DOIUrl":null,"url":null,"abstract":"<p><p><b><i>Purpose:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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 <i>CYP3A5 *3/*</i>3 carriers (<i>P</i>=0.015). No significant association was found between the studied polymorphisms and viral infections and acute graft rejection (<i>P</i>>0.05). <b><i>Conclusion:</i></b> Homozygote <i>CYP3A5 *3/*</i>3 genotype could influence the tacrolimus metabolism rate (C/D ratio).</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"13 2","pages":"393-398"},"PeriodicalIF":3.1000,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278212/pdf/","citationCount":"0","resultStr":"{\"title\":\"The Impact of Single Nucleotide Polymorphisms on the Pharmacokinetics of Tacrolimus in Kidney Allograft Recipients of Northern-West, Iran.\",\"authors\":\"Elaheh Jabbari Hagh, Ali Mousavi, Seyyedeh Mina Hejazian, Mehdi Haghi, Samaneh Esfahanian, Elham Ahmadian, Sepideh Zununi Vahed, Mohammadreza Ardalan\",\"doi\":\"10.34172/apb.2023.038\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b><i>Purpose:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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 <i>CYP3A5 *3/*</i>3 carriers (<i>P</i>=0.015). No significant association was found between the studied polymorphisms and viral infections and acute graft rejection (<i>P</i>>0.05). <b><i>Conclusion:</i></b> Homozygote <i>CYP3A5 *3/*</i>3 genotype could influence the tacrolimus metabolism rate (C/D ratio).</p>\",\"PeriodicalId\":7256,\"journal\":{\"name\":\"Advanced pharmaceutical bulletin\",\"volume\":\"13 2\",\"pages\":\"393-398\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2023-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278212/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advanced pharmaceutical bulletin\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.34172/apb.2023.038\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced pharmaceutical bulletin","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.34172/apb.2023.038","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
The Impact of Single Nucleotide Polymorphisms on the Pharmacokinetics of Tacrolimus in Kidney Allograft Recipients of Northern-West, Iran.
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).