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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 | Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial显示文摘 | Kris V Kowdley Eric Lawitz Israel Crespo Tarek Hassanein Mitchell N Davis Michael DeMicco David E Bernstein Nezam Afdhal John M Vierling Stuart C Gordon Jane K Anderson Robert H Hyland Hadas Dvory-Sobol Di An Robert G Hindes Efsevia Albanis William T Symo | 2013 | The Lancet2013，，9883： | 3 |
| 3 | User acceptance of information technology: toward a unified view 显示文摘 | VENKATESH V MORRIS M G DAVIS G B | 2003 | MIS Quarterly2003，27，3： | 1 |
| 4 | Calibration of near infrared reflectance spectroscopy to estimate nitrogen concentration in potato tissues显示文摘 | YOUNG M W MACKRRON D K L DAVIES H V | 1997 | PotatoResearch1997，，40： | 1 |
| 5 | Deciphering the biology of My cobacterium tuberculosis from the complete genome sequence 显示文摘 | Cole S T Brosch R Parkhill J Gamier T Churcher C Harris D Gordon S V Eiglmeier K Gas S Barry C E Tekaia F Badcock K Basham D Brown D Chillingworth T Cormor R Davies R Devlin K FeltweU T Gentles S Hamlin N Holroyd S Hornsby T Jagels K Kroghs A McLean J Moule S Murphy L Oliver K Osborne J Quail M A Rafandream M A Rogers J Rutter S Seeger K Skelton J Squaraes R Squares S Sulston J E Taylo K Whitehead S Barrell B G | 1998 | Nature1998，393，： | 1 |
| 6 | Calcium anidotrihydroborate:a hydrogen storage material显示文摘 | Diyabalanage H V K Shrestha R P Semelsberger TA Scott B L Bowden M E Davis B L Burrell A K | | 0，，47： | 1 |
| 7 | A computer simulation of multi-ship encounters显示文摘 | DAVIS P V DOVE M J STOCKEL C T | 1982 | Journal of Navigation1982，35，： | 1 |
| 8 | Fluorescent methods for measuring and imaging cytosolic free Ca^2+ in neutrophils显示文摘 | Hallett M B Davies E V Pettit E J | 1996 | Methods1996，9，3： | 1 |
| 9 | Effect of dietary man-nan oligosaccharides and(or)pharmacological additions of cop-per sulfate on growth performance and immunocompetence ofweanling and growing/finishing pigs显示文摘 | Davis M E Maxwell C V Brown D C | 2002 | J Anim Sci2002，80，11： | 1 |
| 10 | Micro fabricated needles for transdermal delivery of macromolecules and nano particles: Fabrication methods and transport studies显示文摘 | MCALLISTER D V WANG P M DAVIS S P | 2003 | PNAS2003，100，13： | 1 |
| 11 | Differential gene up-regulation by hypoxia-inducible factor-1 αlpha and hypoxia-inducible factor-2alpha in HEK293T cells显示文摘 | Wang V Davis DA Haque M | 2005 | Cancer Res2005，65，： | 1 |
| 12 | Arabidopsis and nicotiana antho- cyanin production activated by maize regulators R and Cl 显示文摘 | Lloyd A M Walbot V Davis R W | 1992 | Sci- ence1992，258，： | 1 |
| 13 | Microfabricatedneedles for transdermal delivery of macmmolecules and nanoparticles, fabrication methods and transport studies显示文摘 | Mc?dlister D V Wang P M Davis S P | 2003 | Proc Natl Acad Sci2003，100，13： | 1 |
| 14 | Modeling Landslide Dambreak Flood Magnitudes Case Study显示文摘 | T R Davies V Manville M Kunz | 2007 | Journal of Hydrau lic Engineering2007，133，7： | 1 |
| 15 | User acceptance of information technology: Toward a unified view显示文摘 | Venkatesh V Morris M G Davis G B | 2003 | MIS quarterly2003，，： | 1 |
| 16 | A computer simulation of marine traffic using domains and arenas显示文摘 | DAVIS P V DOVE M J STOCKEL C T | 1980 | Journal of Navigation1980，33，2： | 1 |
| 17 | Empirical atomic sensitivity factors for quantitative analysis by electron spectroscopy for chemical analysis显示文摘 | Wagner C D Davis L E Zeller M V | 1981 | Surf Int Anal1981，3，5： | 1 |
| 18 | In sire formation of lead phosphates in soils as a method to immobilize lead显示文摘 | Ruby M V Davis A Nicholson A | 1994 | Environ Sci Technol1994，28，： | 1 |
| 19 | Climate change and shifts in potential tree species range limits in the Great Lakes region显示文摘 | Walker K V Davis M B Sugita S | 2002 | Journal of Great Lakes Research2002，28，4： | 1 |
| 20 | User Acceptance of Information Technology:Toward a Unified View显示文摘 | Venkatesh V Morris M G Davis G B Davis F D | 2003 | MIS Quarterly2003，27，3： | 1 |
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