Clinical Variants that meet the highest level of criteria, manually curated by PharmGKB, are shown below. Please follow the link in the "Position" column for more information about a particular variant. Each link in the "Position" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.
To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the table.
Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.
The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.
|rs12248560||T (differs from reference)|
|rs11188072||T (differs from reference)|
|rs3758581||G (differs from reference)|
|rs17885098||T (differs from reference)|
PharmGKB haplotype annotations provide information about haplotype-drug 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.
There are direct annotations for this haplotype. Register or sign in to see them.
Based on the ability to metabolize CYP2C19 substrates, individuals can be classified as ultrarapid (UM), extensive (EM), intermediate (IM), or poor metabolizers (PM). EM individuals are homozygous for the CYP2C19*1 allele, which is associated with functional CYP2C19-mediated metabolism. The IM genotype consists of one wild-type allele and one variant allele that encodes reduced or absent enzyme function (e.g., *1/*2, *1/*3), resulting in decreased CYP2C19 activity [Article:12222994]. PM individuals have two loss-of-function alleles (e.g., *2/*2, *2/*3, *3/*3), resulting in markedly reduced or absent CYP2C19 activity [Articles:12222994, 8563772]. Individuals who carry one or two *17 gain-of-function alleles (e.g., *1/*17, *17/*17) may be categorized as UMs. However, the phenotypic consequences of a loss-of-function allele and a *17 compound heterozygous genotype (e.g., *2/*17) is currently unclear but may be in between the EM and IM phenotypes, and possibly substrate-dependent [Articles:20492469, 20233192]. An important caveat in translating genetic information into predicted metabolizer status category is that the CYP2C19*1 allele is defined by the absence of other variants. Thus genotyping assays that do not query all variation in the gene may misclassify some individuals. If all common variants (i.e., >1% allele frequency) are genotyped, misclassification error will be small.
Platelet aggregation inhibitors
Some studies have identified enhanced platelet inhibition and clopidogrel response among UM patients [Articles:20492469, 19106084, 19496924, 20826260] and possibly an increased risk of bleeding complications 20083681; however, other studies have not identified an independent effect of CYP2C19*17 on clopidogrel response [Articles:19106083, 19706858, 18781853]. Despite the heterogeneity in results among individual studies, a recent meta-analysis found CYP2C19*17 to be associated with a lower risk of cardiovascular events and a higher risk of major bleeding [Article:21693476]. However, since the variant that defines the activating allele of *17 and the variant that defines the absence of the *2 allele are in linkage disequilibrium (LD), it is unclear whether there is an independent effect of the *17 allele on platelet aggregation or whether this association is due to the relative absence of the *2 allele in these same patients. Moreover, there is significant LD across the entire CYP2C locus [Article:16132042] and *17 has been identified on haplotypes with both wild-type and variant CYP2C8 alleles depending on ethnicity [Articles:20665013, 20890775].
Proton pump inhibitors (PPIs)
The UM genotype (i.e., *17/*17) has been reported to affect omeprazole pharmacokinetics resulting in increased rates of drug metabolism and subtherapeutic exposure [Article:18294333]. However, not all studies have identified a significant effect of CYP2C19*17 on PPI metabolism and H. pylori eradication [Articles:16912869, 18654768].
Regarding UMs, CYP2C19*17 has been found to correlate with lower serum concentrations of several antidepressants compared to EM patients [Articles:17625515, 20531370, 19884907]; however, the exact clinical relevance of UM genotypes in antidepressant response warrants further investigation.