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tacrolimus and polymorphism

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https://www.readbyqxmd.com/read/27885697/dynamic-effects-of-cyp3a5-polymorphism-on-dose-requirement-and-trough-concentration-of-tacrolimus-in-renal-transplant-recipients
#1
P Chen, J Li, J Li, R Deng, Q Fu, J Chen, M Huang, X Chen, C Wang
WHAT IS KNOWN AND OBJECTIVE: Tacrolimus is a widely used immunosuppressive drug with marked pharmacokinetic variability partly due to CYP3A5 polymorphism. Our study aimed to investigate the dynamic effects of CYP3A5 genotypes on dose requirement and trough concentration (C0 ) of tacrolimus in renal transplant recipients. METHODS: A total of 194 Chinese renal transplant recipients received oral tacrolimus twice daily. Whole-blood C0 of tacrolimus were measured on the 3rd day, 7th day, 14th day, 1st month, 3rd month and 6th month post-transplantation...
November 25, 2016: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/27747372/foxp3-rs3761548-polymorphism-is-associated-with-tacrolimus-induced-acute-nephrotoxicity-in-renal-transplant-patients
#2
Zhuo Wu, Qinxia Xu, Xiaoyan Qiu, Zheng Jiao, Ming Zhang, Mingkang Zhong
PURPOSE: The purpose of this study was to investigate the potential impact of FOXP3 and CCDC22 gene polymorphisms on efficacy and safety of tacrolimus (TAC) in renal transplant patients. METHODS: Genetic polymorphisms were detected in 114 Chinese renal transplant patients who were on TAC-based maintenance immunosuppression and were followed up for at least 2 years. The relationships between FOXP3 rs3761547, rs3761548, rs3761549, rs2232365, rs2280883, and CCDC22 rs2294021 polymorphisms and clinical outcomes such as acute rejection, TAC-induced acute nephrotoxicity, and pneumonia were investigated by using Kaplan-Meier estimates and multivariate Cox regression analysis...
October 17, 2016: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27717793/the-effect-of-cyp3a5-genetic-polymorphisms-on-adverse-events-in-patients-with-ulcerative-colitis-treated-with-tacrolimus
#3
Ayumi Asada, Shigeki Bamba, Yukihiro Morita, Kenichiro Takahashi, Hirotsugu Imaeda, Atsushi Nishida, Osamu Inatomi, Mitsushige Sugimoto, Masaya Sasaki, Akira Andoh
BACKGROUND: Tacrolimus is an immunosuppressive agent, used in the remission induction therapy of ulcerative colitis (UC). AIMS: We investigated the correlation between CYP3A5 genetic polymorphisms and the adverse events in patients with UC. The pharmacokinetics of tacrolimus after oral administration were also analyzed. METHODS: We enrolled 29 hospitalized patients with UC received oral tacrolimus. Genotyping for CYP3A5 A6986G (rs776746) was performed using Custom TaqMan(®) SNP genotyping assays...
September 21, 2016: Digestive and Liver Disease
https://www.readbyqxmd.com/read/27706725/effect-of-pregnane-x-receptor-polymorphisms-on-tacrolimus-blood-concentrations-and-the-resulting-adverse-reactions-in-kidney-transplantation-recipients
#4
Z P Wang, M Zhao, Q S Qu, S Z Miao
We investigated the effect of pregnane X receptor (PXR) polymorphisms on tacrolimus (FK506) blood trough concentrations and the associated adverse reactions in kidney transplantation recipients (KTRs). Polymerase chain reaction (PCR)-restriction fragment length polymorphism was used to detect the genotypes of single nucleotide polymorphism loci in 336 KTRs. The PXR six-base deletion mutation was classified using specific allele PCR, and the FK506 blood trough concentration in the KTRs was measured by chemiluminescent microparticle immunoassay...
September 16, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27597269/predictive-modeling-of-tacrolimus-dose-requirement-based-on-high-throughput-genetic-screening
#5
C Damon, M Luck, L Toullec, I Etienne, M Buchler, B Hurault de Ligny, G Choukroun, A Thierry, C Vigneau, B Moulin, A-E Heng, J-F Subra, C Legendre, A Monnot, A Yartseva, M Bateson, P Laurent-Puig, D Anglicheau, P Beaune, M A Loriot, E Thervet, N Pallet
Any biochemical reaction underlying drug metabolism depends on individual gene-drug interactions and on groups of genes interacting together. Based on a high-throughput genetic approach, we sought to identify a set of covariant single-nucleotide polymorphisms predictive of interindividual tacrolimus (Tac) dose requirement variability. Tac blood concentrations (Tac C0 ) of 229 kidney transplant recipients were repeatedly monitored after transplantation over 3 mo. Given the high dimension of the genomic data in comparison to the low number of observations and the high multicolinearity among the variables (gene variants), we developed an original predictive approach that integrates an ensemble variable-selection strategy to reinforce the stability of the variable-selection process and multivariate modeling...
September 6, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27569929/impact-of-foxp3-polymorphisms-on-the-blood-level-of-tacrolimus-in-renal-transplant-recipients
#6
J Ge, J Wang, H Zhao, K Li, Y Jing, G Li
INTRODUCTION: Tacrolimus is an immunosuppressive medication for organ transplantation. FOXP3(+) T regulatory cells (Tregs) play roles in suppression of rejection and induction of graft tolerance. This study aimed to evaluate the correlation between the polymorphism of FOXP3 and the blood level of tacrolimus in renal transplant recipients. METHODS: This retrospective study included 100 renal transplant recipients receiving tacrolimus treatment and 100 healthy control subjects...
July 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27536671/lupus-nephritis-a-different-disease-in-european-patients
#7
REVIEW
Vladimir Tesar, Zdenka Hruskova
BACKGROUND: Lupus nephritis (LN) is still associated with significant mortality and substantial risk of progression to end-stage renal failure. Its outcome is related to the class and severity of LN and response to treatment, and it is poorer in patients with renal relapses. Ethnicity has a relatively well-defined impact on the outcome of the patients and their response to treatment and must always be taken into consideration in treatment decisions. SUMMARY: In this article, we provide a review of the impact of ethnicity on the prevalence of systemic lupus erythematosus (SLE), the proportion of patients with SLE developing LN, outcomes of SLE and LN and response of LN to treatment...
September 2015: Kidney Diseases
https://www.readbyqxmd.com/read/27536670/lupus-nephritis-in-asia-clinical-features-and-management
#8
REVIEW
Desmond Y H Yap, Tak Mao Chan
BACKGROUND: Lupus nephritis (LN) is a common and severe organ involvement manifesting itself in systemic lupus erythematosus (SLE). There is a considerable difference in prevalence, severity, treatment response and outcomes between Asian LN patients and LN patients from other racial backgrounds. SUMMARY: Asian SLE patients have a higher prevalence of LN than Caucasian SLE patients and often present with a more severe disease. Increasing data from genetic studies, accompanied by progress in high-throughput genotyping, have advanced our knowledge about genetic predispositions that might partly contribute to the clinical variations observed...
September 2015: Kidney Diseases
https://www.readbyqxmd.com/read/27511886/associations-of-the-cyp3a5-3-and-cyp3a4-1g-polymorphisms-with-the-pharmacokinetics-of-oral-midazolam-and-the-urinary-6%C3%AE-hydroxycortisol-cortisol-ratio-as-markers-of-cyp3a-activity-in-healthy-male-chinese
#9
S W Chan, Y Xiao, M Hu, O Q P Yin, T T W Chu, B S P Fok, V H L Lee, B Tomlinson
WHAT IS KNOWN AND OBJECTIVE: The oral plasma clearance of midazolam and the ratio of 6β-hydroxycortisol (6β-OHF) to cortisol (F) in urine are two potential markers for evaluating CYP3A activity in vivo. We assessed the influence of two common CYP3A polymorphisms on the pharmacokinetics of oral midazolam and urinary ratio of 6β-OHF/F in healthy Chinese. METHODS: Single oral 15 mg doses of midazolam were given to 20 healthy male Chinese subjects who were genotyped for the CYP3A5*3 and CYP3A4*1G polymorphisms...
October 2016: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/27503662/pharmacokinetics-of-a-once-daily-dose-of-tacrolimus-early-after-liver-transplantation-with-special-reference-to-cyp3a5-and-abcb1-single-nucleotide-polymorphisms
#10
Yoichi Miyata, Nobuhisa Akamatsu, Yasuhiko Sugawara, Junichi Kaneko, Takehito Yamamoto, Hiroshi Suzuki, Junichi Arita, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Sumihito Tamura, Norihiro Kokudo
BACKGROUND The aim of the present study was to investigate the pharmacokinetics of the once-daily tacrolimus formulation (QD form) in relation to polymorphisms of the donor cytochrome P450 family 3 sub-family A polypeptide 5 (CYP3A5) gene and recipient adenosine triphosphate-binding cassette sub-family B member 1 (ABCB1) gene. MATERIAL AND METHODS A total of 80 consecutive living-donor liver transplant (LDLT) recipients were started on the QD form of tacrolimus (day 1), and 60 patients were completely followed for 7 days early after liver transplantation in order to evaluate the pharmacokinetics...
2016: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/27501475/comparative-performance-of-oral-midazolam-clearance-and-plasma-4%C3%AE-hydroxycholesterol-to-explain-interindividual-variability-in-tacrolimus-clearance
#11
Thomas Vanhove, Hylke de Jonge, Henriëtte de Loor, Pieter Annaert, Ulf Diczfalusy, Dirk R J Kuypers
AIMS: We compared the CYP3A4 metrics weight-corrected midazolam apparent oral clearance (MDZ Cl/F/W) and plasma 4β-hydroxycholesterol/cholesterol (4β-OHC/C) as they relate to tacrolimus (TAC) Cl/F/W in renal transplant recipients. METHODS: For a cohort of 147 patients, 8 h area under the curve (AUC) values for TAC and oral MDZ were calculated besides measurement of 4β-OHC/C. A subgroup of 70 patients additionally underwent intravenous erythromycin breath test (EBT) and were administered the intravenous MDZ probe...
December 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27486667/significant-association-between-toll-like-receptor-gene-polymorphisms-and-posttransplantation-diabetes-mellitus
#12
Jin Sug Kim, Seul Ki Kim, Ji Yoon Park, Yang Gyun Kim, Joo Young Moon, Sang Ho Lee, Chun Gyoo Ihm, Tae Won Lee, Su Kang Kim, Joo-Ho Chung, Sun Woo Kang, Tae Hee Kim, Yeong Hoon Kim, Kyung Hwan Jeong
BACKGROUND: Posttransplantation diabetes mellitus (PTDM) is an important metabolic complication after renal transplantation. Activation of the innate immune system via toll-like receptors (TLRs) is implicated in the pathogenesis of insulin resistance and deficiency. Although links between diabetes, dysregulated innate immune responses, and the TLR signaling pathway have been reported, no study so far has investigated their associations with PTDM. In this study, we ascertained whether single nucleotide polymorphisms (SNPs) in TLRs are associated with PTDM in the Korea population...
2016: Nephron
https://www.readbyqxmd.com/read/27434656/influence-of-the-cyp3a4-5-genetic-score-and-abcb1-polymorphisms-on-tacrolimus-exposure-and-renal-function-in-brazilian-kidney-transplant-patients
#13
Fabiana D V Genvigir, Patricia C Salgado, Claudia R Felipe, Elena Y F Luo, Camila Alves, Alvaro Cerda, Helio Tedesco-Silva, Jose O Medina-Pestana, Nagilla Oliveira, Alice C Rodrigues, Sonia Q Doi, Mario H Hirata, Rosario D C Hirata
BACKGROUND: Polymorphisms in genes encoding transport proteins and metabolizing enzymes involved in tacrolimus (TAC) disposition may be important sources of individual variability during treatment. OBJECTIVE: The aim of this study was to investigate the effect of combined CYP3A4 and CYP3A5 variants, using a CYP3A4/5 genetic score, and ABCB1 polymorphisms on therapeutic TAC monitoring and their relationship with clinical outcomes. MATERIAL AND METHODS: Brazilian kidney transplant recipients (n=151), who received TAC over 3 months after transplantation, were genotyped for CYP3A4 rs2242480 (g...
October 2016: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/27378609/effect-of-abcb1-diplotype-on-tacrolimus-disposition-in-renal-recipients-depends-on-cyp3a5-and-cyp3a4-genotype
#14
T Vanhove, P Annaert, D Lambrechts, D R J Kuypers
The relevance of most genetic polymorphisms beyond CYP3A5*1 on tacrolimus disposition remains unclear. We constructed a predictive mixed model for tacrolimus dose-corrected trough concentration (C0/dose) at months 3, 12 and 24 after transplantation in a retrospective cohort of 766 predominantly Causasian adult renal recipients (n=2042 trough concentrations). All patients were genotyped for 32 single-nucleotide polymorphisms with a proven or possible relevance to tacrolimus disposition based on the previous studies...
July 5, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27320564/long-term-influence-of-cyp3a5-gene-polymorphism-on-pharmacokinetics-of-tacrolimus-and-patient-outcome-after-living-donor-liver-transplantation
#15
H Kato, M Usui, Y Muraki, A Tanemura, Y Murata, N Kuriyama, Y Azumi, M Kishiwada, S Mizuno, H Sakurai, M Okuda, K Nakatani, S Isaji
BACKGROUND: We investigated a long-term association between donor/recipient CYP3A5 polymorphisms, pharmacokinetics of tacrolimus, and recipient outcomes in settings of living donor liver transplantation (LDLT). METHODS: From February 2002 to November 2009, 67 couples of donor/recipients with tacrolimus administration, who could be genotyped for CYP3A5*3 and *1, were eligible in this study. We compared the dose-adjusted trough levels (C/D ratio) and dose/weight ratio of tacrolimus at 1 to 36 months postoperatively and recipient prognosis according to donor/recipient CYP3A5 polymorphisms; *1*1 in 7, *1*3 in 15, and *3*3 in 45, based on recipient genotype, and *1*1 in 1, *1*3 in 28, and *3*3 in 38, based on donor genotype...
May 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27314545/cyp3a-pharmacogenetics-and-tacrolimus-disposition-in-adult-heart-transplant-recipients
#16
Kimberly M Deininger, Anh Vu, Robert L Page, Amrut V Ambardekar, JoAnn Lindenfeld, Christina L Aquilante
BACKGROUND: Cytochrome P450 (CYP) 3A polymorphisms are associated with variable CYP3A metabolizing enzyme activity and tacrolimus pharmacokinetics. We sought to determine the singular and combined impact of CYP3A4*22 and CYP3A5*3 variants on tacrolimus drug disposition in adult heart transplant recipients. METHODS: The retrospective study included 76 patients greater than one year post-heart transplant and receiving tacrolimus. Patients were genotyped for CYP3A4*22 and CYP3A5*3, and combined genotypes were classified as follows: extensive metabolizers (EM, CYP3A4*1/*1+CYP3A5*1 carriers), intermediate metabolizers (IM, CYP3A4*1/*1+CYP3A5*3/*3, or CYP3A4*22 carriers+CYP3A5*1 carriers), and poor metabolizers (PM, CYP3A4*22 carriers+CYP3A5*3/*3)...
September 2016: Clinical Transplantation
https://www.readbyqxmd.com/read/27234753/matrix-metalloproteinase-gene-polymorphisms-and-new-onset-diabetes-after-kidney-transplantation-in-korean-renal-transplant-subjects
#17
S Ong, S-W Kang, Y-H Kim, T-H Kim, K-H Jeong, S-K Kim, Y-C Yoon, S-K Seo, J-Y Moon, S-H Lee, C-G Ihm, T-W Lee, J-H Chung
BACKGROUND: New-onset diabetes after transplantation (NODAT) is a serious metabolic complication that may follow renal transplantation. Matrix metalloproteinases (MMPs) contribute to insulin insufficiency and beta-cell dysfunction in a rat model. The MMP-2 concentrations were lower in patients with type 2 diabetes mellitus, and the plasma MMPs levels were related to diabetes. Similar to the pathogenesis of type 2 diabetes mellitus, insulin resistance and insulin secretion dysfunction occur in patients with the development of NODAT...
April 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27234743/association-interleukin-4-and-interleukin-4-receptor-gene-polymorphism-and-acute-rejection-and-graft-dysfunction-after-kidney-transplantation
#18
H J Lee, T H Kim, S W Kang, Y H Kim, S K Kim, J-H Chung, Y G Kim, J Y Moon, S H Lee, C G Ihm, T W Lee, K H Jeong
BACKGROUND: Cytokine genotypes have previously been studied in patients undergoing solid organ transplantation; certain polymorphisms have been implicated in the development of acute rejection (AR) and graft dysfunction (GD). Allograft outcomes determined, in part, by alloimmune responses is mainly mediated by T-cell responses, activated and driven by cytokines. Interleukin-4 (IL-4) is one such cytokine, which exerts its biological effects through binding to the IL-4 receptor (IL-4R) complex on target cells...
April 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27225724/effects-of-genetic-polymorphism-in-cyp3a4-and-cyp3a5-genes-on-tacrolimus-dose-among-kidney-transplant-recipients
#19
Al-Motassem Yousef, Hisham Qosa, Nailya Bulatova, Ali Abuhaliema, Hussein Almadhoun, Ghada Khayyat, Muhammad Olemat
INTRODUCTION: This study aimed to evaluate the effects of single nucleotide polymorphisms CYP3A4*1B and CYP3A5*3 on tacrolimus dose requirement among kidney transplant recipients. MATERIALS AND METHODS: Blood levels of tacrolimus were measured using microparticle enzyme immunoassay. Genotyping analysis utilized specific polymerase chain reaction-restriction fragment length polymorphism methods for 137 kidney transplant recipients. RESULTS: The median tacrolimus dose was significantly lower in the CYP3A4*1/*1 carriers (0...
May 2016: Iranian Journal of Kidney Diseases
https://www.readbyqxmd.com/read/27221654/interleukin-6-and-rs1800796-locus-single-nucleotide-polymorphisms-in-response-to-hypoxia-reoxygenation-in-hepatocytes
#20
Zhaowen Wang, Shaohan Wu, Jianhua Liao, Lin Zhong, Tonghai Xing, Junwei Fan, Zhihai Peng
Ischemia-reperfusion injury due to hypoxia/reoxygenation (H/R) is one of the main causes of liver damage during liver surgery. Donor interleukin-6 (IL-6) rs1800796 single nucleotide polymorphisms (SNPs) affect the metabolism of tacrolimus following liver transplantation-related hepatic H/R. This study investigated the response of IL-6 and its promoter polymorphisms to hepatic H/R in liver parenchymal cells. The association between IL-6 rs1800796 SNPs and IL‑6 expression was measured in 84 disease-free liver tissues using tissue microarrays and immunohistochemistry...
July 2016: International Journal of Molecular Medicine
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