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SNP and mmf

Xiao-chun Xie, Jun Li, Hong-yang Wang, Hong-liang Li, Jing Liu, Qian Fu, Jia-wen Huang, Chen Zhu, Guo-ping Zhong, Xue-ding Wang, Ping-ping Sun, Min Huang, Chang-xi Wang, Jia-li Li
AIM: To evaluate the effects of UDP-glucuronosyltransferases (UGTs) polymorphisms on the pharmacokinetics of the immunosuppressant mycophenolate mofetil (MMF) in Chinese renal transplant recipients. METHODS: A total of 127 renal transplant patients receiving MMF were genotyped for polymorphisms in UGT1A9 -1818T>C, I399C>T, -118T9/10, -440C>T, -331T>C, UGT2B7 IVS1+985A>G, 211G>T, -900A>G, UGT1A8 518C>G and UGT1A7 622T>C. The plasma concentrations of the MMF active moiety mycophenolic acid (MPA) and main metabolite 7-O-MPA-glucuronide (MPAG) were analyzed using HPLC...
May 2015: Acta Pharmacologica Sinica
Su Kang Kim, Hae Jeong Park, Hosik Seok, Hye Sook Jeon, Tae Won Lee, Sang Ho Lee, Ju Young Moon, Chun Gyoo Ihm, Tae Hee Kim, Yeong Hoon Kim, Sun Woo Kang, Seok Ju Park, Kyung Hwan Jeong, Joo-Ho Chung
Recent studies have shown that single-nucleotide polymorphisms (SNPs) are associated with allograft rejection in kidney transplantation recipients. We evaluated the possible association between SNPs of the cytochrome P450, family 2, subfamily E, polypeptide 1 (CYP2E1) gene, and acute rejection (AR) among renal transplant patients in a Korean population. We conducted a case-control association study in 63 AR and 284 non-AR kidney transplant recipients. The SNPs of CYP2E1 were genotyped by direct sequencing. Recipient sex (p = 0...
June 2014: Clinical Transplantation
Talia Mazidi, Mohammad-Reza Rouini, Mohammad-Hossein Ghahremani, Simin Dashti-Khavidaki, Mahboob Lessan-Pezeshki, Farrokh Lagha Ahmadi, Jamshid Salam-Zadeh, Ali Mandegary, Kheirollah Gholami
There are wide individual differences in pharmacokinetic parameters of mycophenolate mofetil (MMF) among transplanted patients. Some studies have shown that single nucleotide polymorphisms (SNPs) of the Uridine Diphosphate Glucuronosyl Transferase1A9 (UGT1A9) are responsible for these differences in early days after transplantation. Therefore it was decided to evaluate the influence of UGT polymorphism on MMF pharmacokinetics among stable Iranian transplant patients. This was a cross sectional study from March 2008 through December 2008 in Imam Khomeini Hospital affiliated to the Tehran University of Medical Sciences in Iran...
2013: Iranian Journal of Pharmaceutical Research: IJPR
J Pazik, M Ołdak, Z Lewandowski, M Podgórska, E Sitarek, R Płoski, Z Gałazka, A Kwiatkowski, J Malejczyk, M Durlik
BACKGROUND: Uridine diphosphate glucuronosyltransferase (UGT2B7) is responsible for conversion of mycophenolic acid to mycophenolic acyl-glucuronide (acylMPAG). Conflicting data exist regarding the role of UGT2B7 p.His268Tyr (802C>T, rs7439366) variant in the clinical course following organ transplantation. STUDY AIM: The aim of this study was to reveal an association between UGT2B7 p.His268Tyr (802C>T, rs7439366) polymorphism and kidney transplantation outcome...
May 2013: Transplantation Proceedings
Joanna Pazik, Monika Ołdak, Marcin Dąbrowski, Zbigniew Lewandowski, Elżbieta Sitarek, Marta Podgórska, Ewa Ważna, Rafał Płoski, Jacek Szmidt, Andrzej Chmura, Magdalena Durlik, Jacek Malejczyk
BACKGROUND: UDP-glucuronosyltransferases (UGTs) are a group of enzymes involved in the detoxification and excretion of xeno- and endobiotics. Polymorphic variants of the UGT1A9 gene were shown to influence exposition to mycophenolate mophetil (MMF), a common immunosuppressive drug used in kidney allograft recipients. Therefore, the aim of this study was to evaluate an association between key clinical features of kidney post-transplant course in patients receiving MMF therapy and UGT1A9-2152C>T and -275 T>A SNPs, known to induce UGT1A9 gene expression and UGT1A9 98T>C, resulting in reduced enzyme activity...
October 2011: Annals of Transplantation: Quarterly of the Polish Transplantation Society
Erin L Ohmann, Gilbert J Burckart, Yan Chen, Vera Pravica, Maria M Brooks, Adriana Zeevi, Steven A Webber
MMF, the most commonly used adjuvant immunosuppressant in pediatric heart transplantation, has frequent GI adverse events. SNPs in inosine 5'-monophosphate dehydrogenase I (IMPDH1) may contribute to MMF GI intolerance. Phased haplotypes may have more utility than individual SNPs in candidate gene association studies for complex traits. This study defined common IMPDH1 haplotypes and investigated whether these haplotypes influence MMF GI intolerance in 59 pediatric heart recipients. Genotypes were assessed by Taqman analysis of IMPDH1 rs2288553, rs2288549, rs2278293, rs2278294, and rs2228075, and haplotypes were inferred using Arlequin 3...
November 2010: Pediatric Transplantation
Madelon van Agteren, Victor W Armstrong, Ron H N van Schaik, Hans de Fijter, Anders Hartmann, Martin Zeier, Klemens Budde, Dirk Kuypers, Przemyslav Pisarski, Yann Le Meur, Marloes van der Werf, Richard D Mamelok, Michael Oellerich, Teun van Gelder
Mycophenolic acid (MPA) is metabolized primarily by glucuronidation to form the biologically inactive 7-O-glucuronide conjugate (MPAG), which is the major urinary excretion product. MPA is also converted to acyl-glucuronide metabolite (AcylMPAG), which has been suggested to be involved in the generation of MPA-related adverse events such as diarrhea or leucopenia. This conversion of MPA to AcylMPAG is catalyzed by UDP-glucuronosyltransferase 2B7 (UGT2B7). We studied the impact of the -840G>A polymorphisms in the UGT2B7 gene on the pharmacokinetics of AcylMPAG...
August 2008: Therapeutic Drug Monitoring
Dirk R J Kuypers, Hylke de Jonge, Maarten Naesens, Henriette de Loor, Evelyne Halewijck, Marc Dekens, Yves Vanrenterghem
BACKGROUND: Two recent randomized clinical trials--Fixed Dose Versus Concentration Controlled and the Apomygre--evaluating the benefit of therapeutic drug monitoring of mycophenolate mofetil (MMF) in renal allograft recipients reported conflicting results. In both studies, target mycophenolic acid (MPA) AUC(0-12 h) ranges (ie, values used to guide MMF dosing) were derived from a previous study establishing target MPA AUC(0-12 h) ranges in cyclosporine-treated patients between 30 and 60 mg/L x h(-1)...
April 2008: Clinical Therapeutics
Sara Baldelli, Simona Merlini, Norberto Perico, Annalisa Nicastri, Monica Cortinovis, Eliana Gotti, Giuseppe Remuzzi, Dario Cattaneo
INTRODUCTION: The immunosuppressive agent mycophenolic acid (MPA) is metabolized by uridine diphosphate glucuronosyltransferase 1A9 (UGT1A9) to 7-O-glucuronide (MPAG) and excreted by multidrug resistance-associated protein 2 in the bile. By contrast, the production of the acyl MPAG, a minor MPA metabolite, was ascribed to UGT2B7 and UGT1A8. Several polymorphisms in the genes encoding for UGT1A9, UGT2B7 and MRP2 proteins have been described. However, their functional role in vivo on MPA metabolism remains poorly defined...
September 2007: Pharmacogenomics
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