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SNP and tacrolimus

Fabiana D V Genvigir, Alvaro M Nishikawa, Claudia R Felipe, Helio Tedesco-Silva, Nagilla Oliveira, Antony B C Salazar, Jose O Medina-Pestana, Sonia Q Doi, Mario H Hirata, Rosario D C Hirata
STUDY OBJECTIVE: To investigate the influence of single nucleotide polymorphisms (SNPs) in genes encoding metabolizing enzymes (CYP2C8, CYP2J2, and UGT2B7) and transporters (ABCC2 and ABCG2) on dose and/or dose-adjusted trough blood concentrations (C/D ratio), clinical outcomes, and occurrence of adverse events of tacrolimus and mycophenolate sodium in Brazilian kidney transplant recipients. DESIGN: Pharmacogenetic analysis of patients enrolled in a previously published study...
March 17, 2017: Pharmacotherapy
Markus Riegersperger, Max Plischke, Corinna Steinhauser, Anita Jallitsch-Halper, Guerkan Sengoelge, Wolfgang C Winkelmayer, Gere Sunder-Plassmann, Manuela Födinger
BACKGROUND: The multidrug resistance 1 gene (ABCB1) encodes P-glycoprotein (PGP), mainly expressed in the liver and engaged in metabolism of drugs including the immunosuppressant tacrolimus (TAC). ABCB1 single nucleotide polymorphisms (SNP) may significantly alter pharmacokinetics and influence TAC concentrations of kidney transplant recipients (KTR). METHODS: The genotype distribution of ABCB1 1236C>T, 2677G>T/A and 3435C>T was investigated among 96 Austrian KTR who were converted from cyclosporin to TAC...
October 1, 2016: Clinical Laboratory
Heiko Billing, Britta Höcker, Alexander Fichtner, Rita van Damme-Lombaerts, Styrbjorn Friman, Jenö Jaray, Karel Vondrak, Eniko Sarvary, Luca Dello Strologo, Michael Oellerich, Nicolas von Ahsen, Burkhard Tönshoff
BACKGROUND: The pharmacokinetics of tacrolimus (TAC) and mycophenolic acid (MPA) are highly variable. An impact of single-nucleotide polymorphisms (SNPs) of the genes coding for enzymes and transporters involved in the pharmacokinetics of TAC and/or MPA is intuitively conceivable. Accordingly, we sought to analyze the influence of different SNPs on TAC and MPA exposure in pediatric renal transplant recipients. METHODS: A subpopulation of 37 patients (median age: 12...
February 2017: Therapeutic Drug Monitoring
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...
January 2017: Digestive and Liver Disease
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
Milica Kravljaca, Vladimir Perovic, Vera Pravica, Voin Brkovic, Marija Milinkovic, Mirjana Lausevic, Radomir Naumovic
Polymorphisms of the multi drug resistance (MDR1) gene cause variability in P-glycoprotein mediated metabolism of tacrolimus. The aim of this study was to examine the relationship between MDR1 gene single nucleotide polymorphisms (SNPs) and their haplotypes with dosage of tacrolimus in kidney transplant recipients who were cytochrome (CYP) 3A5*3 homozygotes. This study included 91 kidney transplant recipients followed two years after transplantation. Detection and analysis of MDR1 gene polymorphisms in positions C1236T, G2677T/A and C3435T were performed using PCR method...
February 15, 2016: European Journal of Pharmaceutical Sciences
Karim Aouam, Abdessalem Kolsi, Emna Kerkeni, Nadia Ben Fredj, Amel Chaabane, Kamel Monastiri, Naceur Boughattas
AIM: The present study investigated in Tunisian renal transplant patients, genetic polymorphisms of CYP3A4 -392A>G and CYP3A5 6986A>G and their influence on tacrolimus (Tac) pharmacokinetics during early and late post-transplant (PT) phases and established customized ranges of Tac doses matching the C0 target levels according to CYP3A4 and CYP3A5 genotype combination and the PT phase. PATIENTS & METHODS: We included adult Tunisian patients having received Tac for de novo kidney grafts and undergone a therapeutic drug monitoring of Tac by morning C0 monitoring during early (1 to 90 days) and late (over 90 days) PT phases...
December 2015: Pharmacogenomics
Samer K Khaled, Joycelynne M Palmer, Josef Herzog, Tracey Stiller, Ni-Chun Tsai, David Senitzer, Xueli Liu, Sandra H Thomas, Sepideh Shayani, Jeffrey Weitzel, Stephen J Forman, Ryotaro Nakamura
Allelic variants of genes implicated in drug absorption, distribution, metabolism, and excretion (ADME) determine the pharmacokinetic variability of many medications and are increasingly recognized as important factors determining the success or failure of medical treatments. Both tacrolimus and sirolimus have narrow therapeutic ranges maintained by therapeutic drug monitoring (TDM). Using an ADME panel that covers >99% of the PharmaADME working group core list (188 single nucleotide polymorphism [SNP] and 12 copy number variant [CNV] assays in 36 pharmacogenetically relevant genes), we studied 177 patients who underwent allogeneic hematopoietic cell transplantation (HCT) using tacrolimus/sirolimus-based graft-versus-host disease (GVHD) prophylaxis...
February 2016: Biology of Blood and Marrow Transplantation
Brandon A Kohrt, Carol M Worthman, Kerry J Ressler, Kristina B Mercer, Nawaraj Upadhaya, Suraj Koirala, Mahendra K Nepal, Vidya Dev Sharma, Elisabeth B Binder
Despite increased attention to global mental health, psychiatric genetic research has been dominated by studies in high-income countries, especially with populations of European descent. The objective of this study was to assess single nucleotide polymorphisms (SNPs) in the FKBP5 gene in a population living in South Asia. Among adults in Nepal, depression was assessed with the Beck Depression Inventory (BDI), post-traumatic stress disorder (PTSD) with the PTSD Checklist-Civilian Version (PCL-C), and childhood maltreatment with the Childhood Trauma Questionnaire (CTQ)...
2015: International Review of Psychiatry
Wei-Long Shi, Hui-Lin Tang, Suo-Di Zhai
BACKGROUND AND OBJECTIVE: The association between the CYP3A4*1B single nucleotide polymorphism (SNP) and tacrolimus pharmacokinetics in different studies is controversial. Therefore, a meta-analysis was employed to evaluate the correlation between the CYP3A4*1B genetic polymorphism and tacrolimus pharmacokinetics at different post-transplantation times in adult renal transplant recipients. METHODS: Studies evaluating the CYP3A4*1B genetic polymorphism and tacrolimus pharmacokinetics were retrieved through a systematical search of Embase, PubMed, the Cochrane Library, ClinicalTrials...
2015: PloS One
Z Musavi, N Azarpira, M H Sangtarash, M Kordi, K Kazemi, B Geramizadeh, S A Malek-Hosseini
BACKGROUND: New-onset diabetes after transplantation (NODAT) is a serious complication in transplant recipients. Transcription factor-7-like 2 (TCF7L2) is a Wnt signaling-associated transcription factor that plays an important role in β-cell proliferation and insulin secretion. The association between TCF7L2 SNP rs7903146 and NODAT was documented in renal transplant patients. OBJECTIVE: To determine the association between TCF7L2 rs7903146 variants and the risk of NODAT after liver transplantation...
2015: International Journal of Organ Transplantation Medicine
R Schrimpf, J Metzger, G Martinsson, H Sieme, O Distl
In stallions, impaired acrosome reaction (IAR) may often cause subfertility. Single nucleotide polymorphisms (SNPs) within FK506-binding protein (FKBP6) seem to be associated with IAR in stallions. However, their effect on stallion fertility has not yet been quantified. Using whole-genome sequence data of seven stallions, we searched FKBP6 for mutations to perform an association study in Hanoverian stallions with estimated breeding values for the paternal component of the pregnancy rate per oestrus cycle (EBV-PAT) as target trait...
April 2015: Reproduction in Domestic Animals, Zuchthygiene
Jiazhen Xing, Xiaoqing Zhang, Junwei Fan, Bin Shen, Tongyi Men, Jianning Wang
PURPOSE: Interleukin 18 (IL-18) is a potent proinflammatory cytokine thought to down-regulate cytochrome P450 (CYP) enzyme activities. This study aimed to assess the potential influence of two functional single nucleotide polymorphisms (SNPs) in the IL-18 promoter region on the tacrolimus pharmacokinetics in Chinese renal transplant patients. METHODS: We enrolled 96 renal allograft recipients receiving tacrolimus-based immunosuppressive regiments. Two functional SNPs in the IL-18 gene promoter region at the positions -137G/C (rs187283) and -607A/C (rs1946518) and one SNP (rs776746) of CYP3A5 were genotyped using a Mass ARRAY platform...
February 2015: European Journal of Clinical Pharmacology
Joshi Stephen, Katta Mohan Girisha, Ashwin Dalal, Anju Shukla, Hitesh Shah, Priyanka Srivastava, Uwe Kornak, Shubha R Phadke
Osteogenesis imperfecta (OI) is a spectrum of genetic disorders with decreased bone density and bone fragility. Most of the cases of OI are inherited in autosomal dominant fashion with mutations in COL1A1 or COL1A2 genes. Over last few years, twelve genes for autosomal recessive OI have been identified. In this study we have evaluated seven patients with OI from consanguineous Indian families. Homozygosity mapping using SNP microarray was done and selected candidate genes were sequenced. Candidate genes were identified in four out of seven patients studied...
January 2015: European Journal of Medical Genetics
Takashi Fujii, Miho Ota, Hiroaki Hori, Kotaro Hattori, Toshiya Teraishi, Junko Matsuo, Yukiko Kinoshita, Ikki Ishida, Anna Nagashima, Hiroshi Kunugi
The common single nucleotide polymorphism (SNP) rs1360780 (C/T) of the FK506 Binding Protein 5 (FKBP5) gene has been reported to be associated with an altered response of the hypothalamic-pituitary-adrenal (HPA) axis and the development of stress-related psychiatric disorders such as posttraumatic stress disorder (PTSD). In the present study, we examined whether this SNP is associated with cognitive function in a non-clinical population. The full versions of the Wechsler Memory Scale-Revised and Wechsler Adult Intelligence Scale-Revised were administered to 742 and 627 Japanese individuals, respectively, followed by genotyping of rs1360780 by the TaqMan 5'-exonuclease allelic discrimination assay...
2014: Scientific Reports
Yi-kuan Chen, Long-zhi Han, Feng Xue, Cong-huan Shen, Jun Lu, Tai-hua Yang, Jian-jun Zhang, Qiang Xia
Tacrolimus (TAC) is the backbone of an immunosuppressive drug used in most solid organ transplant recipients. A single nucleotide polymorphism (SNP) at position 6986G>A in CYP3A5 has been notably involved in the pharmacokinetic variability of TAC. It is hypothesized that CYP3A5 genotyping in patients may provide a guideline for TAC therapeutic regimen. To further evaluate the impact of CYP3A5 variants in donors and recipients, ABCB1 and ACE SNPs in recipients on TAC disposition, clinical and laboratory data were retrospectively reviewed from 90 pediatric patients with liver transplantation and their corresponding donors after 1 year of transplantation...
2014: PloS One
Alison G Paquette, Barry M Lester, Devin C Koestler, Corina Lesseur, David A Armstrong, Carmen J Marsit
Adverse maternal environments can lead to increased fetal exposure to maternal cortisol, which can cause infant neurobehavioral deficits. The placenta regulates fetal cortisol exposure and response, and placental DNA methylation can influence this function. FK506 binding protein (FKBP5) is a negative regulator of cortisol response, FKBP5 methylation has been linked to brain morphology and mental disorder risk, and genetic variation of FKBP5 was associated with post-traumatic stress disorder in adults. We hypothesized that placental FKBP5 methylation and genetic variation contribute to gene expression control, and are associated with infant neurodevelopmental outcomes assessed using the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scales (NNNS)...
2014: PloS One
Takashi Fujii, Miho Ota, Hiroaki Hori, Kotaro Hattori, Toshiya Teraishi, Daimei Sasayama, Teruhiko Higuchi, Hiroshi Kunugi
FK506 binding protein 5 (FKBP5) is induced by stress and regulates glucocorticoid receptor sensitivity. The T allele of the single nucleotide polymorphism (SNP) FKBP5 rs1360780 (C/T) is associated with an increased risk of post-traumatic stress disorder (PTSD) and reduced hippocampal volume in traumatized or depressed subjects. To examine whether this SNP affects brain structures that regulate stress response, we obtained magnetic resonance imaging data of the brain in 162 healthy subjects using a 1.5 T system...
November 2014: Journal of Psychiatric Research
Eliecer Coto, Beatriz Tavira, Beatriz Suárez-Álvarez, Carlos López-Larrea, Carmen Díaz-Corte, Francisco Ortega, Victoria Alvarez
Tacrolimus (Tac) exhibits an interindividual pharmacokinetic variability that affects the dose required to reach the target concentration in blood. Tac is metabolized by two enzymes of the cytochrome P450 family, CYP3A5 and CYP3A4. The effect of the CYP3A5 genotype on Tac bioavailability has been demonstrated, and the main determinant of this pharmacogenetic effect is a single-nucleotide polymorphism (SNP) in intron 3 of CYP3A5 (6986 A>G; SNP rs776746; also known as CYP3A5*3). The mean dose-adjusted blood Tac concentration was significantly higher among CYP3A5*3 homozygotes than that of carriers of the wild-type allele (CYP3A5*1)...
August 2011: Kidney International Supplements
Akihito Suzuki, Yoshihiko Matsumoto, Ryoichi Sadahiro, Masanori Enokido, Kaoru Goto, Koichi Otani
FK506-binding protein 51 (FKBP5) is a co-chaperone of the glucocorticoid receptor, and plays an important role in the negative feedback regulation of the hypothalamic-pituitary-adrenal axis. The C/T single nucleotide polymorphism in the intron 2 of the FKBP5 gene affects cortisol secretion, and has been implicated in the pathophysiology of depression. In this study, the relationship of the FKBP5 C/T polymorphism with dysfunctional attitudes predisposing to depression was examined. The subjects were 300 healthy Japanese...
August 2014: Comprehensive Psychiatry
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