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| 1 | Thiopurine-methyltransferase variants in inflammatory bowel disease:Prevalence and toxicity in Brazilian patients显示文摘AIM:To analyze the prevalence of thiopurine-methyltransferase(TPMT)genotypes and their associationwith drug toxicity in inflammatory bowel disease(IBD)patients from southeastern Brazil.METHODS:A total of 219 consecutive patients with IBD,of which 146 had Crohn’s disease and 73 had ulcerative colitis,regularly seen at the outpatient unit of the Division of Gastroenterology at the University Hospital Pedro Ernesto of the State University of Rio de Janeiro,a tertiary referral center,were enrolled in this study from February 2009 to January 2011.We analyzed the presence of major TPMT genetic variants(TPMT*2,*3A,*3C)in IBD patients by means of a specific allele and RFLP-PCR.Genomic DNA was isolated from peripheral blood leukocytes by proteinase-K/Sodium Dodecyl Sulfate digestion and phenol-chloroform extraction.TPMT*2(C238G),TPMT*3A(G460A/A719G),and TPMT*3C(A719G)genotypes were detected by real-time polymerase chain reaction followed by direct sequencing with specific primers.Clinical data were systematically recorded,and correlated with the genotype results.RESULTS:The distribution of the selected TPMT gene polymorphism TPMT*2(C238G),TPMT*3A(G460A/A719G),and TPMT*3C(A719G)genotypes was 3.6%,5.4%,and 7.7%of the patients,respectively.Among the side effects recorded from patients taking azathioprine,14 patients presented with pancreatitis and/or an elevation of pancreatic enzymes,while 6 patients had liver toxicity,and 2 patients exhibited myelosuppression/neutropenia.TPMT polymorphisms were detected in 37/219 patients(8 heterozygous for*2,11 heterozygous for*3A,and 18 heterozygous for*3C).No homozygotic polymorphisms were found.Despite the prevalence of the TPMT*3C genotype,no differences among the genotype frequencies were significant.Although no association was detected regarding myelotoxicity or hepatotoxicity,a trend towards the elevation of pancreatic enzymes was observed for TPMT*2 and TPMT*3C genotypes.CONCLUSION:The prevalence of TPMT genotypes was high among Brazilian patients.Variants genes*2and*3C may be associated with azathioprine pancreatic toxicity in a IBD southeastern Brazilian population. | Ana Teresa P Carvalho Barbara C Esberard Renata S B Fróes Davy C M Rapozo Ana B Grinman Tatiana A Simo Juliana C V C Santos Antonio José V Carneiro Luis Felipe Ribeiro-Pinto Heitor S P de Souza | 2014 | World Journal of Gastroenterology2014，20，12： | 3 |
| 2 | Origins of breast cancer subtypes and therapeutic implications 显示文摘 | Sims AH Howell A Howell S J Clarke R B | 2007 | Nature Clin Pract Oncol2007，4，12： | 1 |
| 3 | Nonmehing-flesh trait in peaches is not related to low ethylene production rates显示文摘 | Brovelli E A Brecht J K Sherman W B Sims C A | 1999 | HortScience1999，34，： | 1 |
| 4 | Concepts of plant biotic stress: Some insights into the stress physiology of virus-infected plant from the perspective of photosynthesis 显示文摘 | Balachandran S Hurry V M Kelley S E Osmond C B Robinson S A Rohozinski J Seaton G G R Sims D A | 1997 | Physiologia Plantarum1997，100，： | 1 |
| 5 | Orientation characterization and photoconductive properties of ethylenediamine bridged silicon phthalocyanine polymer thin film显示文摘 | SIM J H ONG B S REED C A | 1996 | Thin Solid Films1996，40，2： | 1 |
| 6 | Changes in cell wall composition during ripening of grape berries显示文摘 | NUNAN K J SIMS IM BACIC A ROBINSON S P F1NCHER G B | 1998 | Plant Physiology1998，118，3： | 1 |
| 7 | B-type natriuretic peptide and mortality in extremely low birth weight infants with pulmonary hypertension:a retrospective cohort analysis显示文摘 | Cuna A Kandasamy J Sims B | 2014 | BMC Pediatr2014，14，： | 1 |
| 8 | Accelerated deployment of an agricultural nutrient management tool:the maryland phosphorus site index显示文摘 | Coale F J Sims J T Leytem A B | 2002 | J Environ Qual2002，31，： | 1 |
| 9 | The Knaster-Kuratowski and Mazurkiewicz theory in hyperconvex metric spaces and some of its applications显示文摘 | Kirk W A Sims B Yuan X Z | 2000 | Nonlinear Anal2000，39，： | 1 |
| 10 | The kine- matic rotating hinge prosthesis for complex knee arthro- plasty显示文摘 | Springer B D Hanssen A D Sim F H | 2001 | Clin Orthop Relat Res2001，，392： | 1 |
| 11 | Defoliation alters the relative contributions of recent and non-recent assimilate to root exudation from Festuca rubra 显示文摘 | Paterson E Thornton B Midwood AJ Sim A | 2005 | Plant Cell Environ2005，28，12： | 1 |
| 12 | Origins of breast cancer subtypes and therapeutic implications 显示文摘 | Sims AH Howell A Howell S J Clarke R B | 2007 | Nature Clin Pratt Oncol2007，4，： | 1 |
| 13 | Contribution of current carbon assimilation in supplying root exudates of Lolium perenne measured using steady-state 13C labelling 显示文摘 | Thornton B Paterson E Midwood AJ Sim A Pratt SM | 2004 | Physiol Plant2004，120，3： | 1 |
| 14 | The Impact of Pollution Charges on Productivity Growth in Canadian Brewing 显示文摘 | Smith J B Sims W A | 1985 | Rand Journal of Eco- nomics1985，16，3： | 1 |
| 15 | Powder coating process parameters for a transfer efficiency model显示文摘 | Chen H Gatlin B Sims R A | 1996 | Particulate Science and Technology1996，，14： | 1 |
| 16 | Effect of clarithromycin on muclear factor-kappa B and transforming growth factor beta in chronic rhino- sinusitis显示文摘 | WALLWORK B COMAN W MACKAY SIM A | 2004 | Larygoscope2004，114，： | 1 |
| 17 | SMART:A stochastic multiscale model for the analysis of energy resources,technology,and policy显示文摘 | Powell W B George A Simã o H | 2012 | INFORMS Journal on Computing2012，24，4： | 1 |
| 18 | Functional characterization of core promoter elements:DPE-specific transcription requires the protein kinase CK2 and the PC4 coactivator显示文摘 | SIMS R J 3RD LANE W S | 2005 | Mol Cell2005，18，： | 1 |
| 19 | Fasting serum triglycerides, free fatty acids, and malondialdehyde are increased in preeclampsia, are positively correlated, and decrease within 48 hours post partum显示文摘 | Hubel C A McLaughlin M K Evans R W Hauth B A Sims C J Roberts J M | 1996 | Am J Obstet Gynecol1996，174，： | 1 |
| 20 | Fixed points of uniformly Lipschitzian mappings 显示文摘 | Dhompongsa S Kirk W A Sims B | 2006 | Nonlinear Anal:TMA2006，65，4： | 1 |
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