rs4244285 in CYP2C19

Clinical Annotations

PharmGKB clinical annotations provide information about variant-drug pairs based on a summary of the individual variant annotations in the database. Therefore, each clinical annotation could represent information from a single paper or multiple papers. The rating system used to assign "Strength of Evidence" levels is described here. The individual variant annotations, including the PMID for each supporting PubMed publication, can be found on the "PGx Research" tab above.

This information is manually curated by PharmGKB. All alleles are displayed on the positive chromosomal strand.

PharmGKB variant annotations provide information about variant-drug pairs or variant-disease pairs based on individual PubMed publications. Each annotation represents information from a single paper and the goal is to report the information that the author states, not an interpretation of the paper. The PMID for supporting PubMed publications is found in the "Evidence" field.

Information presented, including study size, allele frequencies and statistics is taken directly from the publication. However, if the author does not correct p-values in cases of multiple hypotheses, curators may apply a Bonferroni correction. Curators attempt to report study size based on the actual number of participants used for the calculation of the association statistics, so the number may vary slightly from what is reported in the abstract of the paper. OMB Race Category information is derived from the paper and mapped to standardized categories. Category definitions may be found by clicking on the "OMB Race Category" link.

List of all variant annotations for this variant.

Variant Overview

VIP Variant in CYP2C19

rs4244285 (c.681G>A) is the defining polymorphism of the CYP2C19*2 allele (previously referred to as CYP2C19m1) and is a synonymous G>A transition in exon 5 that creates an aberrant splice site. This change alters the mRNA reading frame, which results in a truncated, non-functional protein [Article:8195181]. CYP2C19*2 is the most common CYP2C19 loss-of-function allele, with allele frequencies of approximately 12% in Caucasians, 15% in African-Americans, and 29-35% in Asians [Article:21716271]. For more information see also CYP2C19*2 haplotype page.

Citation	PharmGKB summary: very important pharmacogene information for cytochrome P450, family 2, subfamily C, polypeptide 19. Pharmacogenetics and genomics. 2011. Scott Stuart A, Sangkuhl Katrin, Shuldiner Alan R, Hulot Jean-Sébastien, Thorn Caroline F, Altman Russ B, Klein Teri E.
Reviewed	09/12/2011
Key Publications:
Drugs / Other Molecules	Drug (26) amitriptyline carisoprodol citalopram clomipramine clopidogrel cyclophosphamide hexobarbital imipramine indomethacin lansoprazole mephenytoin methylphenobarbital moclobemide nelfinavir nilutamide omeprazole pantoprazole phenobarbital phenytoin primidone progesterone proguanil propranolol rabeprazole teniposide warfarin

Related Publications

Evidence	Publication
CA	CYP2C19 polymorphism affects single-dose pharmacokinetics of oral pantoprazole in healthy volunteers. European journal of clinical pharmacology. 2012. Gawrońska-Szklarz Barbara, et al.
VA	CYP2C19*2 polymorphism is associated with increased survival in breast cancer patients using tamoxifen. Pharmacogenomics. 2010. Ruiter Rikje, et al.
VA	Effects of genetic defects in the CYP2C19 gene on the N-demethylation of imipramine, and clinical outcome of imipramine therapy. Psychiatry and clinical neurosciences. 1997. Morinobu S, et al.
VA	Genotyping of S-mephenytoin 4'-hydroxylation in an extended Japanese population. Clinical pharmacology and therapeutics. 1996. Kubota T, et al.
VA	Use of omeprazole as a probe drug for CYP2C19 phenotype in Swedish Caucasians: comparison with S-mephenytoin hydroxylation phenotype and CYP2C19 genotype. Pharmacogenetics. 1995. Chang M, et al.
VA	The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. The Journal of biological chemistry. 1994. de Morais S M, et al.

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