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Polymorphism and immunosuppression

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https://www.readbyqxmd.com/read/29454235/donor-and-recipient-p450-gene-polymorphisms-influence-individual-pharmacological-effects-of-tacrolimus-in-chinese-liver-transplantation-patients
#1
Jianyu Liu, Yabo Ouyang, Dexi Chen, Bo Yao, Dongdong Lin, Zhiqiang Li, Yunjin Zang, Huan Liu, Xiaoyue Fu
The immunosuppressant drug tacrolimus (Tac) used for the prevention of immunological rejection is a metabolic substrate of cytochrome P450 enzymes. This study was designed to evaluate the short-term and long-term potential influence of single-nucleotide polymorphisms (SNPs) in CYP450 genes of liver transplant (LT) recipients as well as the donors on individual pharmacological effects of Tac and to guide individualized-medication from the perspective of pharmacogenomics. Twenty-one SNPs of the CYP450 gene were genotyped for both recipients and donors in 373 LT patients receiving Tac-based immunosuppressants...
February 14, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29438108/stat3-enhancing-germline-mutations-contribute-to-tumor-extrinsic-immune-evasion
#2
Daniel Kogan, Alexander Grabner, Christopher Yanucil, Christian Faul, Vijay Kumar Ulaganathan
Immune evasion and the suppression of anti-tumor responses during cancer progression are considered hallmarks of cancer and are typically attributed to tumor-derived factors. Although the molecular basis for the crosstalk between tumor and immune cells is an area of active investigation, whether host-specific germline variants can dictate immunosuppressive mechanisms has remained a challenge to address. A commonly occurring germline mutation (c.1162G>A/rs351855 G/A) in the FGFR4 (CD334) gene enhances STAT3 signaling and is associated with poor prognosis and accelerated progression of multiple cancer types...
February 13, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29423114/germline-polymorphism-of-interferon-lambda3-is-clinically-associated-with-progression-of-renal-cell-carcinoma
#3
Akinori Nukui, Yoshiaki Yanai, Toyonori Tsuzuki, Hideyuki Abe, Kyoko Arai, Ken-Ichiro Yoshida, Takao Kamai
Renal cell carcinoma (RCC) is an immunogenic tumor that shows a metabolic shift to aerobic glycolysis. The immune system can have opposing host-protective and tumor-promoting effects, and aerobic glycolysis suppresses antitumor immunity. In addition to immunostimulatory effect, increasing numbers of studies have revealed that interferon (IFN) is also involved in promoting immunosuppression. Since various single nucleotide polymorphisms (SNPs) can influence the outcome of anticancer therapy, we investigated SNPs for IFN-lambda3, a new member of IFN family, in 53 patients with metastatic RCC who underwent cytoreductive nephrectomy...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29421584/effective-long-term-solution-to-therapeutic-remission-in-inflammatory-bowel-disease-role-of-azathioprine
#4
REVIEW
Lyla Adam, Alisa Phulukdaree, Prashilla Soma
Azathioprine (AZA) is a well-known immunosuppressant used for many years for its ability to ensure long term disease remission in inflammatory bowel diseases (IBD) at an affordable cost to the public. However, the side effect profile has raised many concerns with numerous investigations into the risk, cause and prevention of these effects. Much of the side effect profile of AZA can be linked to a single nucleotide polymorphism (SNP) in the thiopurine methyltransferase (TPMT) gene which ensures the breakdown and efficacy of AZA...
February 5, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29420820/breakthrough-candidemia-after-the-introduction-of-broad-spectrum-antifungal-agents-a-5-year-retrospective-study
#5
Giovanni L Breda, Felipe F Tuon, Jacques F Meis, Patricia F Herkert, Ferry Hagen, Letícia Z de Oliveira, Viviane de Carvalho Dias, Clóvis Arns da Cunha, Flávio Queiroz-Telles
Candidemia is the main invasive fungal disease among hospitalized patients. Several breakthrough candidemia (BrC) cases have been reported, but few studies evaluate the epidemiology, risk factors, molecular characterization, antifungal susceptibility profile and outcome of those patients, especially in developing countries and including patients using broad spectrum antifungals. We conducted a retrospective study from 2011 to 2016, including patients aged 12 years or older with candidemia. Epidemiological characteristics and risk factors for candidemia were evaluated and compared with patients with BrC using univariate and multivariate analysis...
October 9, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/29381954/effect-of-mdr1-c1236t-polymorphism-on-cyclosporine-pharmacokinetics-a-systematic-review-and-meta-analysis
#6
Zhe Chen, Lingli Zhang, Chunsong Yang, Zhimei Jiang, Hongxin Shen, Ge Gui
BACKGROUND: Cyclosporine (CsA) is one of the immunosuppressive drugs, whose pharmacokinetic characteristics vary greatly among individuals. The published data reveal conflicting effects of the polymorphism of MDR1 exon 12 SNP C1236T on the pharmacokinetics of cyclosporine.This study aims to conduct a meta-analysis to investigate the effect of SNP C1236T on the pharmacokinetics of cyclosporine. METHODS: A literature retrieval was conducted to find the relevant papers in databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database (Wan Fang), Chinese Biomedical Literature Database (CBM), VIP Database for Chinese Technical Periodicals (VIP) electronic source for published studies until January 2017...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29345446/the-first-south-american-case-of-pre-implantation-genetic-diagnosis-to-select-compatible-embryo-for-cord-blood-transplantation-as-treatment-for-sickle-cell-anemia
#7
Ciro D Martinhago, Kalina Rn Endo, Mariana A Oliveira, Alex Mm Dias, Gislaine S Pereira, Augusto M Azzolini, Paula Rq Estrada, Caio G Bruzaca, Ana Carolina N Martinhago
Sickle cell anemia is an inherited systemic hemoglobinopathy that affects hemoglobin production in red blood cells, leading to early morbidity and mortality. It is caused by a homozygous nucleotide substitution (c.20A>T) in the β-globin gene (HBB) that changes a glutamic acid to a valine in the protein. We present a case report of a fertile couple, both carriers of the sickle cell anemia mutation, with one affected daughter. Six cycles of assisted reproductive techniques were performed, resulting in 53 embryos in cleavage stage...
January 18, 2018: JBRA Assisted Reproduction
https://www.readbyqxmd.com/read/29330562/influence-of-genetic-polymorphisms-of-il23r-stat3-il12b-and-stat4-on-the-risk-of-aplastic-anemia-and-the-effect-of-immunosuppressive-therapy
#8
Li Zhao, Huanling Zhu, Bing Han, Lixin Wang, Yuming Sun, Xiaojun Lu, Chunyan Huang, Bin Tan, Chunxia Chen, Li Qin
Studies have suggested that IL-23/STAT3 and IL-12/STAT4 signaling pathways associate with aplastic anemia (AA) occurrence. Polymorphisms in pathway-related genes may contribute to AA risk. In the current study, we investigated the association between polymorphisms in genes of IL23R, STAT3, IL12B, and STAT4 and occurrence, severity, and immunosuppressive outcome of AA in the Han population in southwest China. In the current 164 AA cases and 211 controls study, we found T allele and TT genotype of rs7574865 were more frequent in the cases than that in the controls...
January 12, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29329489/mycophenolic-acid-and-its-metabolites-in-kidney-transplant-recipients-a-semimechanistic-enterohepatic-circulation-model-to-improve-estimating-exposure
#9
Malek Okour, Pamala A Jacobson, Mariam A Ahmed, Ajay K Israni, Richard C Brundage
Mycophenolic acid (MPA) is an approved immunosuppressive agent widely prescribed to prevent rejection after kidney transplantation. Wide between-subject variability (BSV) in MPA exposure exists which in part may be due to variability in enterohepatic recirculation (EHC). Several modeling strategies were developed to evaluate EHC as part of MPA pharmacokinetics, however mechanistic representation of EHC is limited. These models have not provided a satisfactory representation of the physiology of EHC in their modeling assumptions...
January 12, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29316067/deep-sequencing-shows-low-level-oncogenic-hepatitis-b-virus-variants-persisting-post-liver-transplant-despite-potent-anti-hbv-prophylaxis
#10
Keith Ck Lau, Carla Osiowy, Elizabeth Giles, Beth Lusina, Guido van Marle, Kelly W Burak, Carla S Coffin
Recent studies suggest that withdrawal of hepatitis B immune globulin (HBIG) and nucleos(t)ide analogues (NA) prophylaxis may be considered in HBV surface antigen (HBsAg) negative liver transplant (LT) recipients with a low risk of disease recurrence. However, the frequency of occult HBV infection (OBI) and HBV variants after LT in the current era of potent NA therapy is unknown. 12 LT recipients on prophylaxis were tested in matched plasma and peripheral blood mononuclear cells (PBMC) for HBV quasispecies by in-house nested PCR and next generation sequencing of amplicons...
January 6, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29283185/genetic-polymorphism-and-decreased-expression-of-hla-class-ii-dp-genes-are-associated-with-hbv-reactivation-in-patients-treated-with-immunomodulatory-agents
#11
Hidetaka Matsuda, Katsushi Hiramatsu, Yu Akazawa, Takuto Nosaka, Yasushi Saito, Yoshihiko Ozaki, Ryoko Hayama, Kazuto Takahashi, Tatsushi Naito, Kazuya Ofuji, Masahiro Ohtani, Tomoyuki Nemoto, Yukio Hida, Hideki Kimura, Yoshihiro Soya, Yasunari Nakamoto
Hepatitis B virus (HBV) reactivation can be triggered by immunosuppressive chemotherapy. HLA class II molecules may play a role in HBV reactivation. Genetic polymorphism and mRNA expression of HLA class II were examined in patients with latent HBV infection treated with immunosuppressive therapies. Subjects with resolved HBV infection who had undergone treatment with immunosuppressive chemotherapies were retrospectively enrolled (n = 42) and divided into reactivated (n = 9) and non-reactivated groups (n = 33)...
December 28, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/29283068/influence-of-genetic-polymorphisms-on-mycophenolic-acid-pharmacokinetics-and-patient-outcomes-in-renal-transplantation
#12
Miao Guo, Zi-Jie Wang, Hai-Wei Yang, Ling Meng, Ruo-Yun Tan, Min Gu, Ji-Fu Wei
Mycophenolic acid (MPA) is an immunosuppressive drug widely used in the treatment of organ transplantation and autoimmune diseases. Pharmacokinetics and pharmacodynamics of MPA varies between individuals, the potential reasons being the genetic polymorphisms in key enzymes, drug transporters and target proteins of MPA, involving uridine diphosphate glucuronosyltransferase enzymes, organic anion transport polypeptides, multidrug resistance-associated protein 2, inosine monophosphate dehydrogenase and others...
December 27, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29279557/effectiveness-of-measuring-genetic-polymorphisms-in-metabolizing-enzymes-of-tacrolimus-within-one-medical-facility
#13
Tomohiro Kaneko, Momoko Arai, Atsushi Watanabe, Shuichi Tsuruoka
OBJECTIVES: Because genetic polymorphisms cause diverse activity in drug metabolizing enzymes, drug concentrations in the blood may be variable among patients. We analyzed the genotypes of CYP3A5 and MDR1, and investigated their relationship with whole blood drug concentrations. METHODS: Eight patients were administered an oral dose of tacrolimus for one week or longer prior to enrollment in this study. Whole blood concentrations for tacrolimus were measured 12 hours post oral administration, on the same day as genotyping, within our hospital using a fully automated gene analyzer...
2017: Journal of Nippon Medical School, Nippon Ika Daigaku Zasshi
https://www.readbyqxmd.com/read/29212248/impact-of-complement-component-3-4-5-single-nucleotide-polymorphisms-on-renal-transplant-recipients-with-antibody-mediated-rejection
#14
Zijie Wang, Haiwei Yang, Miao Guo, Zhijian Han, Jun Tao, Hao Chen, Yuqiu Ge, Ke Wang, Ruoyun Tan, Ji-Fu Wei, Min Gu
Antibody-mediated rejection (ABMR) is an important risk of allograft dysfunction in kidney transplantation. The complement system is considered to be associated with the generation of alloreative antibodies and donor-specific antibodies. However, the association of complement single nucleotide polymorphisms (SNPs) with ABMR still remained unclear. Blood samples of 199 renal transplant recipients containing 68 with ABMR and 131 with stable graft function were collected, and analyzed by next-generation sequencing with an established gene panel...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29146215/-acute-methotrexate-related-neurotoxicity-and-pseudo-stroke-syndrome
#15
V Deneux, N Leboucq, L Saumet, S Haouy, T Akbaraly, N Sirvent
Treatment of acute lymphoblastic leukemia requires high-dose systemic and/or intrathecal methotrexate to prevent and/or treat central nervous system disorders. Acute neurotoxicity of methotrexate, of unknown etiopathogenesis, is characterized by the polymorphism of clinical manifestations, responsible for a potentially harmful diagnostic delay in these immunosuppressed patients. We describe five episodes of transient acute leukoencephalopathy mimicking a stroke, reported in the literature as "pseudo-stroke syndrome"...
November 13, 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/29142307/genetic-polymorphism-related-to-monocyte-macrophage-function-is-associated-with-graft-versus-host-disease
#16
Kati Hyvärinen, Jarmo Ritari, Satu Koskela, Riitta Niittyvuopio, Anne Nihtinen, Liisa Volin, David Gallardo, Jukka Partanen
Despite detailed human leukocyte antigen (HLA) matching and modern immunosuppressive therapy, severe graft-versus-host disease (GvHD) remains a major hurdle for successful allogeneic hematopoietic stem cell transplantation (HSCT). As the genetic diversity in GvHD complicates the systematic discovery of associated variants across populations, we studied 122 GvHD-associated single nucleotide polymorphisms (SNPs) in 492 HLA-matched sibling HSCT donor-recipient pairs from Finland and Spain. The association between these candidate SNPs and grade III-IV acute GvHD and extensive chronic GvHD was assessed...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29140561/interaction-among-smoking-status-single-nucleotide-polymorphisms-and-markers-of-systemic-inflammation-in-healthy-individuals
#17
Thitiya Luetragoon, Lars Erik Rutqvist, Orathai Tangvarasittichai, Bengt-Åke Andersson, Sture Löfgren, Kanchana Usuwanthim, Nongnit Laytragoon Lewin
Cigarette smoke contains toxic and carcinogenic substances that contribute to the development of cancer and various diseases. Genetic variation might be important because not all smokers develop smoking-related disease. The current study addressed the possible interactions among selected single nucleotide polymorphisms (SNPs) in genes related to systemic inflammation, smoking status, the levels of circulating immune response cells and plasma biomarkers of systemic inflammation. Sixty-four healthy blood donors were recruited, of whom 31 were current smokers and 33 were never-users of tobacco products, references...
November 15, 2017: Immunology
https://www.readbyqxmd.com/read/29113092/recipient-hla-g-3142-cc-genotype-and-concentrations-of-soluble-hla-g-impact-on-occurrence-of-cmv-infection-after-living-donor-kidney-transplantation
#18
Hana Guberina, Rafael Tomoya Michita, Sebastian Dolff, Anja Bienholz, Mirko Trilling, Falko M Heinemann, Peter A Horn, Andreas Kribben, Oliver Witzke, Vera Rebmann
The expression modulation of the immunosuppressive non-classical Human leukocyte antigen-G (HLA-G) molecule and its soluble isoforms is an immune evasion strategy being deployed by cytomegalovirus (CMV). The +3142 C>G single nucleotide polymorphism (SNP) located within the 3' untranslated region (3'UTR) is of crucial importance for the regulation of HLA-G expression. Therefore, we analyzed the influence of the +3142 C>G HLA-G SNP on the occurrence of CMV infection in a cohort of 178 living-donor kidney recipients and their 178 corresponding donors...
November 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29103109/polymorphisms-of-nucleotide-factor-of-activated-t-cells-cytoplasmic-2-and-4-and-the-risk-of-acute-rejection-following-kidney-transplantation
#19
Zijie Wang, Haiwei Yang, Shuhui Si, Zhijian Han, Jun Tao, Hao Chen, Yuqiu Ge, Miao Guo, Ke Wang, Ruoyun Tan, Ji-Fu Wei, Min Gu
BACKGROUND: Acute rejection (AR) is a common complication of kidney transplantation. Nuclear factors of activated T cells (NFATs) are transcription factors involved in the activation of T lymphocytes, but their association with AR is unclear. METHODS: This retrospective, case-control study included 200 renal transplant recipients who were divided into the AR group (n = 69) and stable group (n = 131). Their blood samples were collected, and DNA was extracted from the whole blood...
November 4, 2017: World Journal of Urology
https://www.readbyqxmd.com/read/29101067/foxp3-rs3761549-polymorphism-predicts-long-term-renal-allograft-function-in-patients-receiving-cyclosporine-based-immunosuppressive-regimen
#20
Qin-Xia Xu, Xiao-Yan Qiu, Zheng Jiao, Ming Zhang, Ming-Kang Zhong
AIM: The present study was conducted to determine the effect of FOXP3 single nucleotide polymorphisms (SNPs) on clinical outcomes in CsA-treated renal transplant patients. METHODS: A total of 166 renal transplant patients with at least 5years of follow-up were included. SNPs of FOXP3 gene (rs3761547, rs3761548, rs3761549, rs2232365 and rs2280883) were detected by Taqman probe technique. The associations of SNPs with acute rejection, CsA-induced nephrotoxicity, pneumonia and post-transplantation estimated glomerular filtration rate (eGFR) were explored...
October 31, 2017: Gene
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