CYP2C9 and VKORC1 Polymorphisms Are Differently Distributed in the Brazilian Population According to Self-Declared Ethnicity or Genetic Ancestry
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Citações na Scopus
24
Tipo de produção
article
Data de publicação
2012
Título da Revista
ISSN da Revista
Título do Volume
Editora
MARY ANN LIEBERT INC
Autores
SOARES, Renata Alonso Gadi
MACHADO-COELHO, George Luiz Lins
NASCIMENTO, Raimundo Marques do
MILL, Jose Geraldo
Citação
GENETIC TESTING AND MOLECULAR BIOMARKERS, v.16, n.8, p.957-963, 2012
Resumo
Background: Warfarin-dosing pharmacogenetic algorithms have presented different performances across ethnicities, and the impact in admixed populations is not fully known. Aims: To evaluate the CYP2C9 and VKORC1 polymorphisms and warfarin-predicted metabolic phenotypes according to both self-declared ethnicity and genetic ancestry in a Brazilian general population plus Amerindian groups. Methods: Two hundred twenty-two Amerindians (Tupinikin and Guarani) were enrolled and 1038 individuals from the Brazilian general population who were self-declared as White, Intermediate (Brown, Pardo in Portuguese), or Black. Samples of 274 Brazilian subjects from Sao Paulo were analyzed for genetic ancestry using an Affymetrix 6.0 (R) genotyping platform. The CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910), and VKORC1 g.-1639G>A (rs9923231) polymorphisms were genotyped in all studied individuals. Results: The allelic frequency for the VKORC1 polymorphism was differently distributed according to self-declared ethnicity: White (50.5%), Intermediate (46.0%), Black (39.3%), Tupinikin (40.1%), and Guarani (37.3%) (p < 0.001), respectively. The frequency of intermediate plus poor metabolizers (IM + PM) was higher in White (28.3%) than in Intermediate (22.7%), Black (20.5%), Tupinikin (12.9%), and Guarani (5.3%), (p < 0.001). For the samples with determined ancestry, subjects carrying the GG genotype for the VKORC1 had higher African ancestry and lower European ancestry (0.14 +/- 0.02 and 0.62 +/- 0.02) than in subjects carrying AA (0.05 +/- 0.01 and 0.73 +/- 0.03) (p = 0.009 and 0.03, respectively). Subjects classified as IM + PM had lower African ancestry (0.08 +/- 0.01) than extensive metabolizers (0.12 +/- 0.01) (p = 0.02). Conclusions: The CYP2C9 and VKORC1 polymorphisms are differently distributed according to self-declared ethnicity or genetic ancestry in the Brazilian general population plus Amerindians. This information is an initial step toward clinical pharmacogenetic implementation, and it could be very useful in strategic planning aiming at an individual therapeutic approach and an adverse drug effect profile prediction in an admixed population.
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Referências
- Alvim RO, 2010, LIPIDS HEALTH DIS, V9, DOI 10.1186/1476-511X-9-128
- Botton MR, 2011, BRIT J CLIN PHARMACO, V72, P442, DOI 10.1111/j.1365-2125.2011.03942.x
- Caldwell MD, 2008, BLOOD, V111, P4106, DOI 10.1182/blood-2007-11-122010
- Cavallari LH, 2010, CLIN PHARMACOL THER, V87, P459, DOI 10.1038/clpt.2009.223
- Epstein RS, 2011, J AM COLL CARDIOL, V55, P2804
- Ferder NS, 2010, J THROMB HAEMOST, V8, P95, DOI 10.1111/j.1538-7836.2009.03677.x
- Finkelman BS, 2011, J AM COLL CARDIOL, V57, P612, DOI 10.1016/j.jacc.2010.08.643
- Gage BF, 2008, CLIN PHARMACOL THER, V84, P326, DOI 10.1038/clpt.2008.10
- Geisen C, 2005, THROMB HAEMOSTASIS, V94, P773, DOI 10.1160/TH05-04-0290
- Ginsburg GS, 2010, J AM COLL CARDIOL, V55, P2813, DOI 10.1016/j.jacc.2010.04.006
- Giolo SR, 2011, EUR J HUM GENET, V20, P111
- Higashi MK, 2002, JAMA-J AM MED ASSOC, V287, P1690, DOI 10.1001/jama.287.13.1690
- Hirsh J, 2001, CHEST, V119, p8S, DOI 10.1378/chest.119.1_suppl.8S
- JETTER A, 2004, WELSH PAED J, V60, P165, DOI 10.1007/S00228-004-0754-Z
- Johnson JA, 2011, CLIN PHARMACOL THER, V90, P519, DOI 10.1038/clpt.2011.179
- Kirchheiner J, 2004, PHARMACOGENETICS, V14, P19, DOI 10.1097/01.fpc.0000054148.92680.e7
- Kitzmiller JP, 2011, CLEV CLIN J MED, V78, P243, DOI 10.3949/ccjm.78a.10145
- Klein TE, 2009, NEW ENGL J MED, V360, P753
- LANDEFELD CS, 1993, AM J MED, V95, P315, DOI 10.1016/0002-9343(93)90285-W
- Lenzini P, 2010, CLIN PHARMACOL THER, V87, P572, DOI 10.1038/clpt.2010.13
- Li T, 2006, J MED GENET, V43, P740, DOI 10.1136/jmg.2005.040410
- Limdi N, 2008, CLIN PHARMACOL THER, V83, P312, DOI 10.1038/sj.clpt.6100290
- Limdi NA, 2010, BLOOD, V115, P3827, DOI 10.1182/blood-2009-12-255992
- Loebstein R, 2007, BLOOD, V109, P2477, DOI 10.1182/blood-2006-08-038984
- Makdisse M, 2008, ARQ BRAS CARDIOL, V91, P370
- Meyerfreunda D, 2009, J HYPERTENS, V27, P1753, DOI 10.1097/HJH.0b013e32832e0b2b
- Pavani A, 2012, PHARMACOGENOMICS J, V12, P306, DOI 10.1038/tpj.2011.4
- Pena SDJ, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0017063
- Perera MA, 2011, CLIN PHARMACOL THER, V89, P408, DOI 10.1038/clpt.2010.322
- Pimenta JR, 2006, HUM HERED, V62, P190, DOI 10.1159/000096872
- Rieder MJ, 2005, NEW ENGL J MED, V352, P2285, DOI 10.1056/NEJMoa044503
- Santos PCJL, 2011, BMC MED GENET, V12, DOI 10.1186/1471-2350-12-13
- Santos PCJL, 2011, BMC MED GENET, V12, DOI 10.1186/1471-2350-12-136
- Santos PCJD, 2011, AM J HYPERTENS, V24, P278, DOI 10.1038/ajh.2010.244
- SANTOS PCJL, 2012, WELSH PAED J, V68, P273, DOI 10.1007/S00228-011-1125-1
- Santos PCL, 2011, CLIN CHEM LAB MED, V49, P1633, DOI 10.1515/CCLM.2011.654
- Schwarz UI, 2008, NEW ENGL J MED, V358, P999, DOI 10.1056/NEJMoa0708078
- Sconce EA, 2005, BLOOD, V106, P2329, DOI 10.1182/blood-2005-03-1108
- Scott SA, 2011, PHARMACOGENOMICS, V11, P781
- Suarez-Kurtz Guilherme, 2010, Front Pharmacol, V1, P118, DOI 10.3389/fphar.2010.00118
- Suarez-Kurtz G, 2011, BRIT J CLIN PHARMACO, V72, P451, DOI 10.1111/j.1365-2125.2011.04018.x
- Vargens DD, 2011, BASIC CLIN PHARM TOX
- Wu AHB, 2007, PHARMACOGENOMICS, V8, P851, DOI 10.2217/14622416.8.7.851
- You JHS, 2011, EXPERT OPIN PHARMACO, V12, P435, DOI 10.1517/14656566.2011.521153
- Yuan HY, 2005, HUM MOL GENET, V14, P1745, DOI 10.1093/hmg/ddi180