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La farmacogenética, la ciencia que permite identificar las bases genéticas de las diferencias interindividuales en la respuesta a los fármacos, es un tema de gran interés. Los resultados de los diferentes tipos de estudios farmacogenéticos en diferentes campos de la medicina pueden servir para que en un futuro se pueda ofrecer una verdadera medicina personalizada. En este capítulo definimos los conceptos más relevantes de esta disciplina, así como los métodos de estudio utilizados actualmente.
Palabras clave:
Farmacogenética
Farmacogenómica
Polimorfismos genéticos
Pharmacogenetics, the study of how individual genetic profiles influence the response to drugs, is an important topic. Results from pharmacogenetics studies in various clinical settings may lead to personalized medicine. Herein, we present the most important concepts of this discipline, as well as currently-used study methods.
Key words:
Pharmacogenetics
Pharmacogenomics Genetic polymorphisms
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Bibliografía
[1.]
R.B. Altman, T.E. Klein.
Challenges for biomedical informatics and pharmacogenomics.
Annu Rev Pharmacol Toxicol, 42 (2002), pp. 113-133
[2.]
U.A. Meyer.
Pharmacogenetics - five decades of therapeutic lessons from genetic diversity.
Nat Rev Genet, 5 (2004), pp. 669-676
[3.]
L. Kruglyak, D.A. Nickerson.
Variation is the spice of life.
Nat Genet, 27 (2001), pp. 234-236
[4.]
T.R. Bhangale, M.J. Rieder, R.J. Livingston, D.A. Nickerson.
Comprehensive identification and characterization of diallelic insertion-deletion polymorphisms in 330 human candidate genes.
Hum Mol Genet, 14 (2005), pp. 59-69
[5.]
R.P. Ramchandani, Y. Wang, B.P. Booth, et al.
The role of SN-38 exposure, UGT1A1*28 polymorphism, and baseline bilirubin level in predicting severe irinotecan toxicity.
J Clin Pharmacol, 47 (2007), pp. 78-86
[6.]
A.J. Ifrate, L. Feuk, M.N. Rivera, et al.
Detection of large-scale variation in the human genome.
Nat Genet, 36 (2004), pp. 949-951
[7.]
J. Sebat, B. Lakshmi, J. Troge, et al.
Large-scale copy number polymorphism in the human genome.
Science, 305 (2004), pp. 525-528
[8.]
X. Estivill, L. Armengol.
Copy number variants and common disorders: filling the gaps and exploring complexity in genome-wide association studies.
PLoS Genet, 3 (2007), pp. 1787-1799
[9.]
M. Ingelman-Sundberg.
Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity.
Pharmacogenomics J, 5 (2005), pp. 6-13
[10.]
M. Haberl, B. Anwald, K. Klein, et al.
Three haplotypes associated with CYP2A6 phenotypes in Caucasians.
Pharmacogenet Genomics, 15 (2005), pp. 609-624
[11.]
M. Rotger, M. Saumoy, K. Zhang, et al.
Partial deletion of CYP2B6 owing to unequal crossover with CYP2B7.
Pharmacogenet Genomics, 17 (2007), pp. 885-890
[12.]
International HapMap Consortium.
The International HapMap Project.
Nature, 426 (2003), pp. 789-796
[13.]
International HapMap Consortium.
A haplotype map of the human genome.
Nature, 437 (2005), pp. 1299-1320
[14.]
K.A. Frazer, D.G. Ballinger, International HapMap Consortium, et al.
A second generation human haplotype map of over 3.1million SNPs.
Nature, 449 (2007), pp. 851-861
[15.]
H.Y. Yuan, J.J. Chiou, W.H. Tseng, et al.
FASTSNP: an always up-to-date and extendable service for SNP function analysis and prioritization.
Nucleic Acids Res, 34 (2006), pp. W635-W641
[16.]
L. Conde, J.M. Vaquerizas, H. Dopazo, et al.
PupaSuite: finding functional single nucleotide polymorphisms for large-scale genotyping purposes.
Nucleic Acids Res, 34 (2006), pp. W621-W625
[17.]
B.M. Hemminger, B. Saelim, P.F. Sullivan.
TAMAL: an integrated approach to choosing SNPs for genetic studies of human complex traits.
Bioinformatics, 22 (2006), pp. 626-627
[18.]
V.E. Carlton, J.S. Ireland, F. Useche, M. Faham.
Functional single nucleotide polymorphism-based association studies.
Hum Genomics, 2 (2006), pp. 391-402
[19.]
M. Rotger, H. Tegude, S. Colombo, et al.
Predictive value of known and novel alleles of CYP2B6 for efavirenz plasma concentrations in HIV-infected individuals.
Clin Pharmacol Ther, 81 (2007), pp. 557-566
[20.]
E.J. Topol, K.A. Frazer.
The resequencing imperative.
Nat Genet, 39 (2007), pp. 439-440
[21.]
S. Romeo, L.A. Pennacchio, Y. Fu, et al.
Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL.
Nat Genet, 39 (2007), pp. 513-516
[22.]
E.S. Lander, L.M. Linton, B. Birren, et al.
Initial sequencing and analysis of the human genome.
Nature, 409 (2001), pp. 860-921
[23.]
J.C. Venter, M.D. Adams, E.W. Myers, et al.
The sequence of the human genome.
Science, 291 (2001), pp. 1304-1351
[24.]
J.B. Fan, M.S. Chee, K.L. Gunderson.
Highly parallel genomic assays.
Nat Rev Genet, 7 (2006), pp. 632-644
[25.]
K.L. Gunderson, F.J. Steemers, G. Lee, L.G. Mendoza, M.S. Chee.
A genome-wide scalable SNP genotyping assay using microarray technology.
Nat Genet, 37 (2005), pp. 549-554
[26.]
J.N. Hirschhorn, M.J. Daly.
Genome-wide association studies for common diseases and complex traits.
Nat Rev Genet, 6 (2005), pp. 95-108
[27.]
W.Y. Wang, B.J. Barratt, D.G. Clayton, J.A. Todd.
Genome-wide association studies: theoretical and practical concerns.
Nat Rev Genet, 6 (2005), pp. 109-118
[28.]
J. Fellay, K.V. Shianna, D. Ge, et al.
A whole-genome association study of major determinants for host control of HIV-1.
Science, 317 (2007), pp. 944-947
[29.]
P. Kelly, N. Stallard, Y. Zhou, J. Whitehead, C. Bowman.
Sequential genome-wide association studies for monitoring adverse events in the clinical evaluation of new drugs.
Stat Med, 25 (2006), pp. 3081-3092
[30.]
Kindmark A, Jawaid A, Harbron CG, et al. Genome-wide pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests an underlying immune pathogenesis. Pharmacogenomics J. 2007 (en prensa).
[31.]
L.L. Warren, A.R. Hughes, E.H. Lai, et al.
Use of pairwise marker combination and recursive partitioning in a pharmacogenetic genome-wide scan.
Pharmacogenomics J, 7 (2007), pp. 180-189
[32.]
D.J. Balding.
A tutorial on statistical methods for population association studies.
Nat Rev Genet, 7 (2006), pp. 781-791
[33.]
J.R. Gibbs, A. Singleton.
Application of genome-wide single nucleotide polymorphism typing: simple association and beyond.
PLoS Genet, 2 (2006), pp. e150
[34.]
D. Kasperaviciute, M.E. Weale, K.V. Shianna, et al.
Large-scale pathways-based association study in amyotrophic lateral sclerosis.
Brain, 130 (2007), pp. 2292-2301
[35.]
R. Lubomirov, C. Csajka, A. Telenti.
ADME pathway approach for pharmacogenetic studies of anti-HIV therapy.
Pharmacogenomics, 8 (2007), pp. 623-633
[36.]
S.T. Bennett, C. Barnes, A. Cox, L. Davies, C. Brown.
Toward the 1,000 dollars human genome.
Pharmacogenomics, 6 (2005), pp. 373-382
[37.]
D.R. Bentley.
Whole-genome re-sequencing.
Curr Opin Genet Dev, 16 (2006), pp. 545-552
[38.]
H. Bayley.
Sequencing single molecules of DNA.
Curr Opin Chem Biol, 10 (2006), pp. 628-637
[39.]
E.R. Mardis.
Anticipating the 1,000 dollar genome.
Genome Biol, 7 (2006), pp. 112
[40.]
R.F. Service.
Gene sequencing. The race for the $1000 genome.
Science, 311 (2006), pp. 1544-1546
[41.]
H. Wolinsky.
The thousand-dollar genome. Genetic brinkmanship or personalized medicine?.
EMBO Rep, 8 (2007), pp. 900-903
[42.]
C.A. Hutchison III.
DNA sequencing: bench to bedside and beyond.
Nucleic Acids Res, 35 (2007), pp. 6227-6237
[43.]
F. Innocenti, S.D. Undevia, L. Iyer, et al.
Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan.
J Clin Oncol, 22 (2004), pp. 1382-1388
[44.]
F. Innocenti, M.J. Ratain.
Pharmacogenetics of irinotecan: clinical perspectives on the utility of genotyping.
Pharmacogenomics, 7 (2006), pp. 1211-1221
[45.]
S.B. Haga, K.E. Thummel, W. Burke.
Adding pharmacogenetics information to drug labels: lessons learned.
Pharmacogenet Genomics, 16 (2006), pp. 847-854
[46.]
B.F. Gage, L.J. Lesko.
Pharmacogenetics of warfarin: regulatory, scientific, and clinical issues.
J Thromb Thrombolysis, 25 (2008), pp. 45-51
[47.]
CDER US-FDA. Information for Healthcare Professionals Carbamazepine (marketed as Carbatrol, Equetro, Tegretol, and generics). 12/12/2007. Disponible en: http://www.fda.gov/cder/drug/InfoSheets/HCP/carbamazepineHCP.htm (acceso el 18/12/2007).
[48.]
S. Mallal, E. Phillips, G. Carosi, J.M. Molina, C. Workman, J. Tomazic, E. Jägel-Guedes, S. Rugina, O. Kozyrev, J.F. Cid, P. Hay, D. Nolan, S. Hughes, A. Hughes, S. Ryan, N. Fitch, D. Thorborn, A. Benbow, PREDICT-1 Study Team.
HLA-B* 5701 screening for hypersensitivity to abacavir.
N Engl J Med, 358 (2008), pp. 568-577
[49.]
J.J. Swen, T.W. Huizinga, H. Gelderblom, et al.
Translating pharmacogenomics: challenges on the road to the clinic.
PLoS Med, 4 (2007), pp. e209
[50.]
I. Grossman.
Routine pharmacogenetic testing in clinical practice: dream or reality?.
Pharmacogenomics, 8 (2007), pp. 1449-1459
[51.]
L.J. Lesko.
Personalized medicine: elusive dream or imminent reality?.
Clin Pharmacol Ther, 81 (2007), pp. 807-816
[52.]
L.M. Baudhuin, L.J. Langman, D.J. O’Kane.
Translation of pharmacogenetics into clinically relevant testing modalities.
Clin Pharmacol Ther, 82 (2007), pp. 373-376
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