Implementation and utilization of genetic testing in personalized medicine

Figures & data

Table 1 Candidate genes for pharmacogenetic implementation with available practice guidelines and recommendation statements

Gene(s)	Drug	Organization	Practice guidelines/recommendation statements
CFTR	Ivacaftor	CPIC	Clancy et al; 2014^Citation118
CYP2C9/VKORC1	Warfarin	ACMG	Flockhart et al; 2008^Citation119
		CPIC	Johnson et al; 2011^Citation120
CYP2C19	Clopidogrel	CPIC	Scott et al; 2011,^Citation121 2013^Citation122
		ACCF/AHA	Holmes et al; 2010^Citation123
	TCAs	CPIC	Hicks et al; 2013^Citation124
CYP2D6	Codeine	CPIC	Crews et al; 2012^Citation125
	SSRIs	CPIC	In preparation; 2014a
		EGAPP	EGAPP Working Group; 2007^Citation70
	Tamoxifen	ACMG	Lyon et al; 2012^Citation126
	TCAs	CPIC	Hicks et al; 2013^Citation124
CYP3A	Tacrolimus	CPIC	In preparation; 2014a
DPYD	Fluoropyrimidine	CPIC	Caudle et al; 2013^Citation127
HLA-B	Abacavir	CPIC	Martin et al; 2012^Citation128
	Allopurinal	CPIC	Hershfield et al; 2013^Citation129
	Carbamazepine	CPIC	Leckband et al; 2013^Citation130
	Phenytoin	CPIC	In preparation; 2014a
IFNL3 (IL28B)	Interferon-α	CPIC	Muir et al; 2014^Citation131
SLCO1B1	Simvastatin	CPIC	Wilke et al; 2012^Citation132
TPMT	Azathioprine/6-mercaptopurine	CPIC	Relling et al; 2011,^Citation133 2013^Citation134
UGT1A1	Irinotecan	EGAPP	EGAPP Working Group; 2009^Citation71
Multiple (eleven genes)	Multiple (53 drugs)	KNMP-PWG	Swen et al; 2011^Citation72

Note:

a Based on information available from Pharmacogenomics Knowledge Base website (http://www.pharmgkb.org/cpic/pairs), and K Caudle, CPIC Coordinator, personal communication.

Abbreviations: TCA, tricyclic antidepressants; SSRI, selective serotonin reuptake inhibitors; ACCF, American College of Cardiology Foundation; ACMG, American College of Medical Genetics and Genomics; AHA, American Heart Association; CPIC, Clinical Pharmacogenetics Implementation Consortium; EGAPP, Evaluation of Genomic Applications in Practice and Prevention; KNMP-PWG, Royal Dutch Association for the Advancement of Pharmacy-Pharmacogenetics Working Group.

Table 2 Pharmacogenetic tests approved by the US FDA for IVD usea

Gene(s)	Assay	Alleles interrogated	Company	Date approved
CYP2C9 and VKORC1	Verigene^® Warfarin Metabolism Test	CYP2C9*2, *3, VKORC1 c.174-136C>T (1173C>T)	Nanosphere, Inc.	September 2007
	INFINITI^® Warfarin Assay	CYP2C9*2, *3, VKORC1 c.-1639G>A	AutoGenomics, Inc.	January 2008
	eSensor^® Warfarin Sensitivity Test	CYP2C9*2, *3, VKORC1 c.-1639G>A	GenMark Diagnostics, Inc.	July 2008; December 2011
	eQ-PCR™ LC Warfarin Genotyping Kit	CYP2C9*2, *3, VKORC1 c.-1639G>A	TrimGen Corporation	February 2009
CYP2C19	AmpliChip^® CYP450 Test	*2, *3	Hoffmann-La Roche Ltd	January 2005
	INFINITI^® CYP2C19 Assay	*2, *3, *17	AutoGenomics, Inc.	October 2010
	Verigene^® CYP2C19 Test	*2, *3, *17	Nanosphere, Inc.	November 2012
	Spartan RX CYP2C19 Assay	*2, *3, *17	Spartan Bioscience Inc.	August 2013
	xTAG^® CYP2C19 Kit v3	*2, *3, *17	Luminex Molecular Diagnostics, Inc.	September 2013
CYP2D6	AmpliChip^® CYP450 Testb	*2–*11, *15, *17, *19, *20, *29, *35, *36, *40, *41, duplication	Hoffmann-La Roche Ltd	January 2005
	xTAG^® CYP2D6 Kit v3	*2–*11, *15, *17, *29, *35, *41, duplication	Luminex Molecular Diagnostics, Inc.	May 2013

Notes:

a As listed on the US FDA IVD Product Database: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/default.htm

b the CYP2D6 star (*) allele nomenclature for the AmpliChip^® is based on the available nomenclature at the time of product release. The *41 allele reported by the AmpliChip^® is not consistent with the current *41 haplotype nomenclature as it does not interrogate the 2988G>A variant that was discovered after the development of the Amplichip^®.¹³⁵

Abbreviations: FDA, Food and Drug Administration; IVD, in vitro diagnostic.

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