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Polymorphism and liver transplant

Hiroshi Yamazaki
Research over the past 30 years has elucidated the roles of polymorphic human liver cytochrome P450 (P450) enzymes associated with toxicological and/or pharmacological actions. Thalidomide exerts its various pharmacological and toxic actions in primates through multiple mechanisms, including nonspecific modification of many protein networks after bioactivation by autoinduced human P450 enzymes. To overcome species-differences between rodents, currently, nonhuman primates and/or mouse models with transplanted human hepatocytes are used...
October 17, 2016: Chemical Research in Toxicology
M Khosravi, I Saadat, M H Karimi, S A Malek Hosseini
BACKGROUND: Acute rejection is the main problem in liver transplantation that occurs in the first days or months of transplantation. It includes histological and cellular rejection. Acute histological rejection is confirmed by biopsy. Glutathione S-transferase family is the most important genes in phase II detoxification working in xenobiotic and drug metabolism. GSTO2 is one of the members of this family. GSTO2 (N142D) polymorphism may influence metabolism of immunosuppressive drugs...
2016: International Journal of Organ Transplantation Medicine
Paul M K Gordon, Aneal Khan, Umair Sajid, Nicholas Chang, Varun Suresh, Leo Dimnik, Ryan E Lamont, Jillian S Parboosingh, Steven R Martin, Richard T Pon, Jene Weatherhead, Shelly Wegener, Debra Isaac, Steven C Greenway
Cell-free DNA (cfDNA) has significant potential in the diagnosis and monitoring of clinical conditions. However, accurately and easily distinguishing the relative proportion of DNA molecules in a mixture derived from two different sources (i.e., donor and recipient tissues after transplantation) is challenging. In human cellular transplantation, there is currently no useable method to detect in vivo engraftment, and blood-based non-invasive tests for allograft rejection in solid organ transplantation are either non-specific or absent...
2016: Frontiers in Cardiovascular Medicine
Hansjörg Thude, Maike Janssen, Martina Sterneck, Björn Nashan, Martina Koch
Expression of human leukocyte antigen G (HLA-G) has been associated with increased graft survival and decreased rejection episodes. It has been described that the HLA-G 14-base pair (bp) insertion/deletion (ins/del) (rs66554220) and +3142C>G (rs1063320) gene polymorphisms modify the expression level of HLA-G. The aim of the study was to investigate whether these HLA-G polymorphisms have an impact on acute rejection after liver transplantation. In total, 146 liver transplant recipients (57 with acute rejection and 89 without acute rejection) and 99 corresponding liver donors were genotyped for both polymorphisms...
September 21, 2016: Human Immunology
Hideaki Kagaya, Takenori Niioka, Mitsuru Saito, Takamitsu Inoue, Kazuyuki Numakura, Tomonori Habuchi, Shigeru Satoh, Masatomo Miura
1. The objective of this study was to examine the association of UGT1A9, SLCO, ABCC polymorphisms with mycophenolic acid (MPA) pharmacokinetics in ABO blood type (ABO) incompatible patients with severe renal dysfunction pre-transplantation. 2. In all patients, on day 14 after beginning mycophenolate mofetil (MMF) treatment (1 week before transplantation) and on day 28 after renal transplantation, samples were collected just prior to and 1, 2, 3, 4, 6, 9 and 12 hours after oral MMF administration. 3. The median dose-adjusted AUC0-12 of MPA after renal transplantation was significantly lower than before transplantation (57...
September 10, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Sunaina Tejpal Karna, Chandra Kant Pandey, Vijay Kant Pandey, Mandeep Dhankhar
No abstract text is available yet for this article.
August 2016: Indian Journal of Anaesthesia
Katja Piras-Straub, Khaleda Khairzada, Peri Kocabayoglu, Andreas Paul, Guido Gerken, Kerstin Herzer
The cytokine tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis in liver cancer cells but not in normal liver cells. Therefore, TRAIL got credited to play a role in hepatocellular carcinoma (HCC) development and progression. Impaired expression of TRAIL in HCC cells and sequence variations in the TRAIL promoter may facilitate development, growth, and spread . The TRAIL promoter was sequenced from liver tissue of 93 patients undergoing partial liver resection (PRT) or liver transplantation (LT) for HCC...
August 31, 2016: Cancer Medicine
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
Nadezda R Maksimova, Elizaveta E Gurinova, Aitalina L Sukhomyasova, Anastasia L Danilova, Vladimir S Kaimonov, Mira T Savvina, Aleksandra E Yakovleva, Elena I Alekseeva
INTRODUCTION: Tyrosinemia type 1 (HT1) (OM IM 276700) is an inborn error of tyrosine catabolism caused be fumarylacetoacetate hedralase deficiency (FAH). In tyrosinemia type I, dietary therapy and nitisinone (Orfandin®), liver transplantation are effective . AIM: We present here the first report on identification of FAH mutation in HT1 Yakut patient from Russia with a novel one. MATERIAL AND METHODS: The material for the clinical study is based on the genetic data of the patient card with tyrosinemia type 1, which is observed in the medical-genetic consultations Republican Hospital №1-National Medical Center of the Republic of Sakha (Yakutia)...
2016: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
Juntao Ke, Shuaidan Zeng, Jianxiong Mao, Jianyao Wang, Jiao Lou, Jiaoyuan Li, Xueqin Chen, Cheng Liu, Liu-Ming Huang, Bin Wang, Lei Liu
BACKGROUND: Biliary atresia (BA) is a major neonatal cholestatic disease and main indication for pediatric liver transplantation in the world. Recently, GPC1 has been implicated as a risk gene for BA by genetic studies and follow-up functional experiments on zebrafish. METHODS: Two common genetic variants of GPC1, rs2292832 and rs3828336, were selected systematically through 'SNPinfo', and were examined using TaqMan Genotyping Assays for association studies in a Chinese population containing 134 cases and 618 controls...
October 2016: Journal of Pediatric Surgery
Dawei Chen, Shuanghai Liu, Sheng Chen, Zhaowen Wang, Zehua Wu, Kai Ma, Junwei Fan, Zhihai Peng
BACKGROUND: Application of the Milan criteria is an effective strategy to select patients with hepatocellular carcinoma (HCC) for liver transplantation, but HCC recurrence is still a major concern. The aim of this study was to determine whether interleukin 6 (IL6) polymorphisms and clinical variables are potential predictors for HCC recurrence and prognosis after transplantation. METHODS: A total of 110 consecutive patients with HCC undergoing liver transplantation were enrolled in the study...
July 1, 2016: International Journal of Clinical Oncology
T Matsui, M Usui, K Fujinaga, K Nakatani, Y Iizawa, H Kato, A Tanemura, Y Murata, Y Azumi, N Kuriyama, M Kishiwada, S Mizuno, H Sakurai, S Isaji
BACKGROUND: Late renal dysfunction (LRD) is known to be one of the most important complications to affect long-term outcome after living-donor liver transplantation (LDLT). The relationship between angiotensin-converting enzyme insertion (I)/deletion (D) gene polymorphism and renal function after LDLT are still unknown. The aim of this study was to elucidate the risk factors for LRD after LDLT, focusing on ACE gene polymorphism. MATERIALS AND METHODS: Among the 94 recipients who underwent adult-to-adult LDLT between March 2002 and September 2009, the total number of subjects who survived more than 1 year after LDLT and in whom angiotensin-converting enzyme genotype could be measured was 64...
May 2016: Transplantation Proceedings
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
Pu-Sen Wang, Jing Kuai, Hao Li, Chun-Guang Wang, Bao-Jie Shi, Lin Zhong
BACKGROUND: Mannose-binding lectin 2 (MBL2) plays a key role in the host immune response, but whether it is associated with hepatocellular carcinoma (HCC) is not clear. The present study aimed to identify the association between MBL2 gene polymorphisms and HCC in patients with hepatitis B virus (HBV)-related cirrhosis in the Chinese population. METHODS: A single-nucleotide polymorphism of MBL2, rs11003123, was genotyped and analyzed in a case-control study of HBV-related cirrhotic patients with HCC (n=77) and without HCC (n=40)...
June 2016: Hepatobiliary & Pancreatic Diseases International: HBPD INT
M H Starczewska, D Giercuszkiewicz, J Piwowarska, G Kostrzewa, G Niewinski, M Krawczyk, A Kanski
No abstract text is available yet for this article.
December 2015: Intensive Care Medicine Experimental
Jiali Zhou, Yani Liu, Xiaomei Luo, Rufei Shen, Chunxiao Yang, Tingyu Yang, Shaojun Shi
The activation of Ras-related C3 botulinum toxin substrate 1 (Rac1) is critical in the renal, hepatic and cardiac diseases that lead to the requirement for transplantation, however, no investigations have been performed in Chinese populations to determine the association between RAC1 genotypes and the activation of Rac1. In the present study, 304 solid organ transplant recipients (SOTRs), consisting of 164 renal transplantations, 85 hepatic transplantations and 55 cardiac transplantations, and 332 Chinese healthy control subjects were recruited to investigate whether differences existed in the mRNA and protein expression levels of Rac1 in the different groups...
August 2016: Molecular Medicine Reports
King-Wah Chiu, Toshiaki Nakano, Kuang-Den Chen, Chih-Che Lin, Tsung-Hui Hu, Shigeru Goto, Chao-Long Chen
To investigate the effect of IL28B single nucleotide polymorphisms (SNPs) (rs8099917 and rs12979860) in the donors and recipients on the outcome of Hepatitis C virus-RNA clearance after living donor liver transplantation (LDLT). The rs8099917 and rs12979860 genotypes in 50 donor and recipients pairs were explored on the pre-operative day (POD) and post-operative day 30 (POD30). There was a significant difference in HCV-RNA clearance before (12%, 6/50) and after (48%, 24/50) liver transplantation (P < 0.001)...
2016: PloS One
Nicolás Martínez-Calle, Ana Alfonso, José Rifón, Ignacio Herrero, Pedro Errasti, Gregorio Rábago, Juana Merino, Ángel Panizo, Javier Pardo, Felipe Prósper, Ricardo García-Muñoz, Ramón Lecumberri, Carlos Panizo
This retrospective study evaluates the impact of rituximab on PTLD response and survival in a single-centre cohort. PTLD cases between 1984 and 2009, including heart, kidney, liver and lung transplant recipients, were included. Survival was analysed taking into account the type of PTLD (monomorphic vs. polymorphic), EBV infection status, IPI score, Ann Arbor stage and use of rituximab. Among 1335 transplanted patients, 24 developed PTLD. Median age was 54 yr (range 29-69), median time to diagnosis 50 months (range 0-100)...
May 27, 2016: European Journal of Haematology
Hideya Kamei, Taro Nakamura, Shunji Nagai, Masatoshi Ishigami, Nobuyuki Hamajima
OBJECTIVES: Liver transplant in patients with preexisting portal vein thrombosis involves complicated surgical procedures and increased blood loss, indicating the need for further surgical innovations to overcome these difficulties. Patients who are at high risk of developing portal vein thrombosis may benefit from prophylactic anticoagulant therapy while on the transplant wait list. Homozygosity for C677T polymorphism in the methylenetetrahydrofolate reductase gene has been associated with a high plasma homocysteine concentration, which is a risk factor for venous thrombosis...
June 2016: Experimental and Clinical Transplantation
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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