GENETIC POLYMORPHISMS OF CYTOCHROME P450 (CYP) 2C19 ©2010 Pharmacology Weekly Inc
Allele	Population	Single Nucleotide Polymorphism	Location	Activity	Notes
CYP2C191*	General Population	Wild-type; 50,720bp	10q24.1-3	Normal	Extensive metabolizer
CYP2C192*	2-5% Caucasians 18-23% Japanese	40bp deletion (681G→A)	Exon 5	↓	Poor metabolizer
CYP2C193*	13% Islands of Vanuatu	W212X(636G→A)	Exon 4	↓	Poor metabolizer; premature stop codon
CYP2C194*	0.6-3% Caucasians	M1V (Mutation in initiation codon A→G	Initiation codon	↓	Poor metabolizer, Defect in initiation codon
CYP2C195*	Low in both Chinese & Japanese	R433W (1297C→T)	Exon 9	↓	Poor metabolizer
CYP2C1917*	18% Ethiopians & Swedes, 1.3% Japanese, 0.64% Chinese	C806T (3402C→T)	5'-flanking region	↑	Ultra-rapid metabolizer Increased 2C19 gene transcription

Note: A = adenine (nucleotide), C = cystine (nucleotide), G = guanine (nucleotide), M = methionine (amino acid), R = arginine (amino acid), T = thymine (nucleotide); V = valine (amino acid); W = tryptophan (amino acid); X = termination codon.

Pharmacology Weekly CYP2C19 Related Publications

What influences do genetic polymorphisms to cytochrome P450 (CYP) 2C19 have on cardiovascular disease (CVD) outcomes in patients taking clopidogrel (Plavix)? PW Pharmacogenet Newsl 2009;1(7):1-5. Link to Answer & Summary of Studies

Are there any differences among the proton pump inhibitors (PPI) in their ability to inhibit the activation of clopidogrel (Plavix) through the cytochrome P450 (CYP) enzyme system? PW Drug Interact Newsl 2009;1(24):1-6. Link to Answer

What studies are available related to the drug interaction between proton pump inhibitors (PPI) and clopidogrel (Plavix) on cardiovascular (CV) related endpoints or outcomes? PW Drug Interact Newsl 2009;1(25):1-5. Link to Answer

What data are available regarding the efficacy of clopidogrel (Plavix) on platelet inhibition or reactivity when given with a proton pump inhibitor (PPI)? PW Drug Interact Newsl 2009;1(26):1-5. Link to Answer

Are there any updates to the drug interaction between clopidogrel (Plavix) and proton pump inhibitors in patients who have received percutaneous coronary intervention (PCI) involving stent placement? PW Drug Interact Newsl 2009;1(45):1-5. Link to Answer & Summary of Studies

What are the common genetic polymorphisms to cytochrome P450 (CYP) 2C19 that could impact drug metabolism? PW Pharmacogenet Newsl 2010;2(3):8-11. Link to Answer

References to Table

Meier UT, Meyer UA. Genetic polymorophism of human cytochrome P-450 (S)-mephenytoin 4-hydroxylase: studies with human autoantibodies suggest a functionally altered cytochrome P-450 isoenzyme as cause of the genetic deficiency. Biochemistry 1987;26:8466-8474. PubMed

De Morais SMF, Wilkinson GR, Blaisdell J et al. Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanses. Molec Pharmacol 1994;46:594-8. PubMed

De Morais SMF, Wilkinson GR, Blaisdell J et al. The major genetic defect responsible for the polymoprhism of S-mephenytoin metabolism in humans. J Biol Chem 1994;269:15419-15422. PubMed

Kaneko A, Kaneko O, Taleo G et al. High frequencies of CYP2C19 mutations and poor metabolism of proguanil in Vanuatu. Lancet 1997;349:921-2. PubMed

Ferguson RJ, DeMorais SMF, Benhamou S et al. A new genetic defect in human CYP2C19: mutation of the initiation codon is responsible for poor metabolism of S-mephenytoin. J Pharmacol Exp Ther 1998;284:356-361. PubMed

Sim SC, Risinger C, Dahl ML et al. A common novel CYP2C19 gene variant causes ultra-rapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin Pharmacol Ther 2006;79:103-113. PubMed

Sugimoto K, Uno T, Yamazaki H et al. Limited frequency of the CYP2C19*17 allele and its major role n a Japanese population. Br J Clin Pharmacol 2008;65:437-39. PubMed

Pharmacology Weekly

Pharmacology Weekly CYP2C19 Related Publications

References to Table

Clinical Resources

Stay Connected

Share This Page

SEARCH
Advanced Search