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Microsoft word - cyp2c19 overview and ordering information v2_cmgdl.docx

CYP2C19 Genotyping Assay: Genetics and Clinical Overview

Test Information:
CYP2C19 Genotyping Assay (CMGDL test code 4001)
For sample collection, transport and testing information refer to the CMGDL website
See the link for additional test ordering information such as CPT codes, test methodology and limitations.
Genetics, Epidemiology and Clinical
Genotype allelic combinations and related
Cytochrome P450 2C19, CYP2C19, is an isoenzyme Genetic variations in the CYP2C19 gene lead to of the cytochrome P450 super family and plays an inappropriate concentrations of drugs and drug important role in the metabolism of many commonly used metabolites, which may contribute to toxicity and risk of drugs # (Wang, 2011). Large inter-individual differences adverse drug reactions or lack of therapeutic benefit. have been observed in the metabolism of these drugs in Determining the CYP2C19 genotype can help by vivo, and individuals can be divided into normal (also called “extensive” metabolizer, EM), intermediate  CYP2C19 Extensive (Normal) Metabolizer metabolizer (IM), poor metabolizers (PMs), and ultra- (EM): when no mutations are detected by the rapid metabolizers (UM). These differences can primarily genotyping assay, presence of normal *1 alleles be attributed to CYP2C19 genetic polymorphisms (de is suggested. Normal CYP2C19 enzyme activity and normal metabolizer phenotype is expected The CYP2C19 gene has nine exons and is located on when two normal *1 alleles are considered to be chromosome 10. To date, more than thirty CYP2C19 Single Nucleotide Polymorphisms (SNPs), from which  CYP2C19 Intermediate to Normal Metabolizer: over twenty haplotypes were identified, are presented on this phenotype is suggested by the presence of CYP2C19 allele nomenclature website one CYP2C19 allele with no function (eg *2 or ( ). Genetic *3) or one CYP2C19 allele with decreased variations in the CYP2C19 gene are inherited in an autosomal recessive pattern of inheritance with a  CYP2C19 Intermediate Metabolizer (IM): this penetrance that is drug dependent (Mega et al., 2009; phenotype is suggested by the presence of two Simon et al., 2009; Nakamoto et al., 2007; Wang, 2011). CYP2C19 alleles with decreased function or one CYP2C19 mutation frequency varies among different CYP2C19 allele with decreased function and one ethnicities. The most predominant genetic defects CYP2C19 non-functional allele; responsible for the PM phenotype result from two SNPs,  CYP2C19 Poor Metabolizer (PM): this CYP2C19*2 (c.681G>A) and CYP2C19*3 (c.636G>A). phenotype is suggested by the presence of two In studies of PMs across global populations, these two SNPs have been proposed to explain anywhere from less  CYP2C19 Rapid and Ultra-Rapid Metabolizer than 50% to more than 90% of the PM phenotype (UM): this phenotype is suggested by the (Nakamoto et al., 2007). The *2 allele is found in presence of one or two CYP2C19 non-functional approximately 30% of Asians and 15% of Caucasians and African-Americans. The *3 allele is present in approximately 8% of Asians and is present less than 1% Clinical Significance and Test Indications
of Caucasians and African-Americans. A PM phenotype The clinical impact of the CYP2C19 genotype is (ie the presence of two non-functional CYP2C19 alleles) influenced by whether a drug is activated (e.g. is approximately present in 4% of Caucasians, 5% of clopidogrel, tamoxifen) or inactivated (e.g. amitryptiline, CYP2C19*17 (-808C>T) causes an increase in Involvement of other metabolic pathways, and other transcriptional activity, resulting in ultra-rapid non-genetic factors such as concurrent intake of other metabolism of CYP2C19 substrates (Sim et al., 2006; medications may also influence the clinical impact of the Clinical Molecular Genetics Diagnostic Laboratory
University of Miami · PO Box 019132 (M860) · Miami, FL 33101 Location: 1501 NW 10 Ave, Biomedical Research Building Room 445 (M860) ·Miami, FL 33136 Ph: 1-305-243-6671 Fax: 1-305-243-8368 Email: This test is indicated in patients candidate or Related Tests (visit our website at
undergoing drug therapy with drugs metabolized by the CYP2C19 isoenzyme. The test may also be indicated for Clopidogrel Sensitivity CYP2C19 Genotyping assay patients with personal or family history positive for adverse effects to drugs metabolized by CYP2C19. In particular, the test may be indicated if the following drugs References
( -Home Page of the Human Cytochrome P450 (CYP) Allele Clopidogrel (Plavix®) (instead of test code 4001, order
Nomenclature Committee ( “Clopidogrel Sensitivity CYP2C19 Genotyping assay”,
( Clopidogrel is an antiplatelet drug used in -Becquemont L et al (2011). Practical recommendations for pharmacogenomics-based prescription: 2010 ESF-UB Conference on atherothrombotic diseases, such as myocardial infarction Pharmacogenetics and Pharmacogenomics. Pharmacogenomics. 2011 and stroke, which is an inactive prodrug that needs to be -De Morais (1994a) Identification of a new genetic defect responsible Among persons treated with clopidogrel, carriers of for the polymorphism of (S)-mephenytoin metabolism in Japanese. Mol Pharmacol 46:594–598. CYP2C19 reduced-function alleles had significantly lower -De Morais (1994b). The major genetic defect responsible for the levels of the active metabolite of the drug, diminished polymorphism of S-mephenytoin metabolism in humans. J Biol Chem platelet inhibition, and a higher rate of subsequent cardiovascular events than did non carriers (Mega et al., -Mega JL et al (2009). Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med 360:354–362. 2009; Simon et al., 2009). An increase in the daily dose is -Nakamoto K et al (2007). Genotyping and haplotyping of CYP2C19 somehow a possibility although the best advice is to functional alleles on thin-film biosensor chips. Pharmacogenet consider changing clopidogrel for a CYP2C19- independent drug (e.g. prasugrel or ticagrelor) -Rudberg I (2008). Impact of the ultrarapid CYP2C19*17 allele on serum concentration of escitalopram in psychiatric patients. Clin (Becquemont L et al, 2011), in particular for carriers of two non-functional alleles (e.g. *2 and/or *3). -Sibbing D et al (2009). CYP450 2C19 loss-of-function polymorphism Monitoring of platelet function may also be considered. and stent thrombosis following percutaneous coronary intervention. Eur. In contrast, the CYP2C19*17 allele has been Heart J. 30(8), 916–922. -Sibbing D et al (2010). Cytochrome 2C19*17 allelic variant, platelet significantly associated with an enhanced response to aggregation, bleeding events, and stent thrombosis in clopidogrel-treated clopidogrel and an increased risk of bleeding (Sibbing et patients with coronary stent placement. Circulation 121:512–518. -Sim SC et al (2006). A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin Pharmacol Ther 79:103–113 -Simon T et al. (2009). Genetic determinants of response to clopidogrel Antidepressants such as Amitriptyline and Escitalopram
and cardiovascular events. N Engl J Med 360:363–375. Determining the CYP2C19 genotype, in combination -Wang H et al. (2011). Evaluation of the Effects of 20 Nonsynonymous with drug monitoring once therapy is initiated, may help Single Nucleotide Polymorphisms of CYP2C19 on S-Mephenytoin 4’Hydroxylation and Omeprazole 5’Hydroxylation. Drug Metab If a patient carries the CYP2C19 *2 or *3 alleles -Wedlund PJ (2000). The CYP2C19 enzyme polymorphism. higher plasma concentrations of the drug and  If a patient carries the CYP2C19 *17 alleles may show lower plasma concentrations and higher The following is a list of drugs metabolized through the CYP2C19 enzyme that may be affected by these variants: proton pump inhibitors (lansoprazole, omeprazole, Tamoxifen
antiepileptics (diazepam, phenytoin(O), S-mephenytoin, If a patient carries the CYP2C19*17 alleles higher phenobarbital, R-mephobarbital, primidone); concentrations of the active metabolite endoxifen are antidepressants (amitriptyline, citalopram, clomipramine, imipramine, moclobemide); produced, with decreased breast cancer recurrence when anti-thrombotics (R-warfarin, clopidogrel); NSAIDs treated with tamoxifen. Note that the response to tamoxifen is not expected to be affected by decrease antimicrobials (chloramphenicol, pentamidine); function alleles such as the CYP2C19 *2 allele. others (carisoprodol, cyclophosphamide, hexobarbital, nelfinavir, nilutamide, progesterone, proguanil, propranolol, teniposide, Voriconazole). Please note that this is not an all-inclusive list. DR. JOHN T. MACDONALD FOUNDATION DEPARTMENT OF HUMAN GENETICS
Leonard M. Miller School of Medicine · PO Box 019132 (M860) · Miami, FL 33101 Location: 1501 NW 10 Ave, Biomedical Research Building (M860) ·Miami, FL 33136 Ph: 1-305-243-6671 Fax: 1-305-243-8368 Email:



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CURRICULAM VITAE S. SYED JAHAN , 8/149 – Middle Street MANDAPAM – 623 518 Educational Qualification • Pursuing M. Sc., Zoology, Annamalai University Annamalai Nagar, • B. Sc., Zoology, Jamal Mohammed College Bharathidasan University Technical and other qualification • Typewriting junior grade 1990, Department of Technical Education, Tamil Nadu • Typewriting s

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