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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 | A recombinant human angiostatin protein inhibits experimental primary and metastatic cancer 显示文摘 | Sim B K L O'Reilly M S Liang H | 1997 | Cancer Research1997，57，： | 2 |
| 3 | 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 |
| 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 | Blends of synthetic and natural polymers as drug delivery systems for growth hormone 显示文摘 | Downes B Sim S | 1995 | Biomaterials1995，16，7： | 1 |
| 6 | A parametric formulation of the generalized spectral subtraction method 显示文摘 | Sim B L Tong Y C Chang J S | 1998 | IEEE Trans on Speech and Audio Pro- cessing1998，6，4： | 1 |
| 7 | Influence of dietary energy source on performance and fatty liver syn- drome in White Leghorn laying hens显示文摘 | Bragg D B Sim J S Hodgson G C | 1973 | Poult Sci1973，52，2： | 1 |
| 8 | 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 |
| 9 | 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 |
| 10 | Field performance of transgenic cotton containing the Bt gene显示文摘 | Stone T B Sims S R Marron P G J | 1989 | Proc Invertebr Pathol1989，53，： | 1 |
| 11 | Internet-based teleoperation of an intelligent robot with optimal two-layer fuzzy controller显示文摘 | Sim K B Byun K S Harashima F | 2006 | IEEE Transactions on Industrial Electronics2006，53，4： | 1 |
| 12 | Dependence of osteoblastic response on variations in the chemical composition and physical properties of hydroxyapatite显示文摘 | BEST S SIM B KAYSER M | 1997 | J Mater Sci: Mater in Med1997，8，： | 1 |
| 13 | Analytical Prediction of Chatter Stability for Variable Pitch and Variable Helix Milling Tools 显示文摘 | SIMS N D MANN B HUYANAN S | 2008 | Journal of Sound and Vibration2008，317，345： | 1 |
| 14 | A recombinant human angiostatin protein inhibits experimental primary and metastatic cancer显示文摘 | SIM B K L O'REILLY M S LIANG H | 1998 | Cancer Res1998，57，： | 1 |
| 15 | Effect of dietary saponin on egg cholesterol level and laying hen performance显示文摘 | Sim J S Kitts W D Bregg D B | 1984 | Cana- dian Journal of Animal Science1984，64，4： | 1 |
| 16 | Effects of fabrication procedures on fatigue resistance of welded joints in steel ortho- tropic decks显示文摘 | CHARLES S SIM H B UANG C M | 2009 | Journal of Bridge Engineering2009，14，5： | 1 |
| 17 | Structure activity relationship of antioxidative property of flavonoids and inhibitory effect on matrix metalloproteinase activity in UVA- irradiated human dermal fibroblast 显示文摘 | Sim G S Lee B C Cho H S | 2007 | Archives of Pharmacal Research2007，30，3： | 1 |
| 18 | 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 |
| 19 | A combined genetic algorithms-shooting method approach to solving optimal control problems 显示文摘 | SIM Y C LENG S B SUBRAMANIAN V | 2000 | Int J of Systems Science2000，31，1： | 1 |
| 20 | Structural and opto- electronic properties of SnO2 nanowires synthesized from ball-milled SnO powders 显示文摘 | LEE J S SIM S K MIN B | 2004 | J Cryst Growth2004，267，12： | 1 |
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