2006 FDA advisory committee plans to hold an advisory meeting to consider changing tamoxifen labeling to recommend that all women prescribed tamoxifen be tested for CYP2D6 genotype (October 2006).
2006 A variant of 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMGCR) gene in African Americans (who have the allele at 30% frequency compared to 2% in European Americans) may account for variable response to the statins that are used to treat cardiovascular disease. Two hapolotypes of HMGCR in African Americans reduce response to statins. (Krauss group: Circulation 112 (17) Supplement II:725 (Abstract))
2006 PharmGKB has 1940 registered users; 95 phenotype submissions; 64 genes with data; 5540 unique variants; 12,710 subjects with genotypes; 5305 subjects with genotype/phenotype data; 141,759 phenotypes measured; 1391 literature annotations; 1,316,994 genotype-phenotype pairs
2006 CYP2A6 genotype predicts likelihood of smoking cessation in response to nicotine patches (Benowitz group: Apr 2006 Mol Psychiatry 11:400-409; Jun 2006 Clin Pharmacol Ther 79:600-608)
2005 PharmGKB has 1900 registered users; 264 PK/PD genes with data; 5540 unique variants; 113 phenotype submissions; 40,000 Web site visitors/month
2005 Examined 137 patients with torsades de point and 700 controls to find 2 genome-wide risk alleles for long QT syndrome (Roden group: Oct 2005 Circulation Abstract)
2005 Polymorphisms in beta2-adrenergic receptor are associated with survival among patients who receive beta-blocker therapy after a heart attack (McLeod group: Sep 28. 2005 JAMA 294:1526-1533)
2005 A new method avoids multiple comparison problems in whole genome analysis. (Weiss group: Jul 2005 Nature Genetics 37:683-691).
2005 Variants in the gene for vitamin K epoxide reductase complex 1 (VKORC1) affect response to the anticoagulant warfarin (McLeod group: Jun 2, 2005 NEJM 352:2285-2293)
2005 Polymorphisms of beta-1 receptor associated with reduced effect on ejection fraction of beta adrenergic blocking agents (Johnson group: Mar 2005 Clin Pharmacol Ther 77:127-137, Apr 2005 Pharmacogenet Genomics 15:227-234)
2005 The FDA issues guidelines encouraging pharmaceutical companies to gather and submit information on how genetic variations affect drug response (March 2005)
2005 Nicotine elimination rate is found to be highly heritable (Benowitz group: Feb 2005 Pharmacogenet Genomics 15:115-125)
2004-2006 Functional annotation of about 90 SNPs in 12 membrane transporters in the SLC and ABC superfamilies (Giacomini group: Feb 2006 Genome Res 16:223-230)
2004-2006 Predictors of ALL relapse identified using candidate genes and genome-wide approaches (Relling group: 2004 NEJM 351:533-542; 2005 Cancer Cell 7:375-386; 2005 Blood 105:4752-4758, 2006 Blood 107:843-844)
2004 Polymorphism in beta-2 receptor is associated with reduced response to beta-2 agonists used to treat asthma (Weiss group: Oct 2004 J Allergy Clin Immunol 114:747-754)
2004 Discovery that variations in CRHR1 affects how asthmatics respond to steroids (Weiss group: Jul 1, 2004 Hum Mol Genet 13:1353-1359)
2004 PharmGKB has 64 PK/PD genes with data; 2100 unique variants; 95 phenotype submissions
2004 A genetic variant in UGT1A1 is associated with severe neutropenia. Discovery results in FDA-mandated change in irinotecan labeling. (Ratain group: Apr 15, 2004 J Clin Oncol 22:1382-1388)
2003-2006 Genetic variations in CYP2D6 affect endoxifen levels and clinical outcomes in those treated with tamoxifen. Ultimately, clinical guidelines are changed to disallow the use of SSRIs with tamoxifen. (Flockhart group: Dec 3, 2003 JNCI 95:1758-1764; Jan 5, 2005 JNCI 97:30-39; Dec 20, 2005 J Clin Oncol 23:9312-9318; Jul 2006 Clin Pharmacol Ther 80:61-74)
2003 SSRIs, common antidepressants, are shown to block the metabolism of tamoxifen to endoxifen by CYP2D6 (Flockhart group: Dec 3, 2003 JNCI 95:1758-1764)
2003 Pharmacogenetic studies introduced to mouse phenome project (McLeod group: Oct 2003 J Appl Physiol 95:1352-1360)
2003 Polymorphisms of beta-1 receptor are associated with lower anti-hypertensive response to beta adrenergic blocking agents (Johnson group: Jul 2003 Clin Pharmacol Ther 74:44-52)
2003 About 550 novel SNPs are discovered in 25 membrane transporter genes (Giacomini group: May 13 2003 PNAS 100:5896-5901)
2003 PharmGKB has 1000 literature annotations
2002 PharmGKB has 120 registered users and 2200 Web site visitors/month
2002 Newly identified mutations in potassium channel genes account for 5 to 10 percent of drug-induced long QT syndrome (Roden group: Apr 23 2002 Circulation 105:1943-1948)
2000 Endoxifen is identified as the active metabolite of tamoxifen (Flockhart group: Dec 3, 2003 JNCI 95:1758-1764)
2000 A potassium channel polymorphism is associated with drug-induced long QT syndrome (Roden group: Sep 12 2000 PNAS 97:10613-10618)
2000 The NIH Pharmacogenetics Research Network constructs the PharmGKB web site, the first comprehensive compilation of pharmacogenetics knowledge
2000 A draft of the human genome sequence is completed
2000 African Americans are shown to have reduced response to cholesterol-lowering statins (Krauss group: Epub Jan 27 2000 Am J Cardiol 97:843-850)
1999 Genetic variation of UGT1A1 is associated with SN38 glucuronidation and irinotecan toxicity (Ratain group: May 1999 Clin Pharmacol Ther 65:576-582)
1998 Smokers with CYP2A6 polymorphism are found to smoke less (Benowitz group: Jun 25 1998 Nature 393:750)
1997-2006 Genetic variants in a number of methyltransferases, including COMT and HNMT, are discovered and characterized (Weinshilboum group: 1996 Pharmacogenetics 6:243-250; 1998 Mol Pharmacology 53:708-717)
1997 First human organic cation and purine nucleoside transporters are cloned (Giacomini group: Jun 1997 Mol Pharmacol 51:913-921; Dec 1997 Am J Physiol 273:F1058-1065)
1995 First inactivating polymorphism identified for TPMT (Relling group: Feb 14 1995, PNAS 92:949-953)
1993-1996 TPMT gene is cloned and a variant allele is found (Weinshilboum group: 1993 Mol Pharmacology 43:878-887; 1996 Cell Biology 15:17-30)
1991 Pharmacogenetic testing becomes standard in St. Jude acute lymphoblastic leukemia (ALL) trials (Relling group: 1999 Science 286:487-491; 2000 Leukemia 14:567-572; 2006 Blood 107:843-844)
1990s The extent of glucuronidation of SN38 is shown to correlate with toxicity of the anticancer drug irinotecan (Ratain group: 1994 Cancer Res 54:3723-3725; 1998 J Clin Invest 101:847-854)
1987-1989 Low TPMT activity is associated with an increased risk for myelosuppression—the suppression of bone marrow activity as a side effect of cancer treatments (Weinshilboum group: 1987 Clinical Pharmacol Therapeutics 41:18-25; 1989 Clinical Pharmacol Therapeutics 46:149-154)
1980s Clinical features of drug-induced long QT syndrome, a life-threatening form of cardiac arrhythmia, are defined (Roden group: Jun 1985 Circ Res 56:857-867; Jun 1986 Am Heart J 111:1088-1093; Jul 1986 J Am Coll Cardiol 8:73A-78A 1986)
1980 First genetic polymorphism identified in thiopurine S-methyltransferase (TPMT), a gene involved in drug metabolism (Weinshilboum group: Sep 1980 Am J Hum Genet 32:651-662)
