Annotation of CYP2C19*1, CYP2C19*2, CYP2C19*3

CYP2C19 *2/*2 + *3/*3 is associated with decreased clearance of rabeprazole in healthy individuals as compared to CYP2C19 *1/*1 + *1/*2 + *1/*3.

Healthy individuals (negative for Helicobacter pylori) with the *2/*2 or *3/*3 genotype had decreased apparent oral clearance (CL/F; units = mL*kg/min), increased area under the concentration-time curve from 0-24 hours (AUC0-24; units = ng*h/mL) and increased maximum plasma concentration (Cmax; units = ng/mL) of rabeprazole, as compared to those with the *1/*1, *1/*2 or *1/*3 genotype. No significant association was seen for terminal elimination half-life (t1/2; units = hours). Please note that these genotypes were referred to by their previous designations of m1 (*2) and m2 (*3).

Gene

CYP2C19

Phenotype Category

Metabolism/PK

Association Significance

The study reports this association is significant

PharmGKB ID

1183618419

Evidence for Clinical Annotations

This annotation has been used as evidence for the following clinical annotations.

    Study Parameters

    1.

    Study type

    cohort

    Study size

    15

    Association p-value

    = 0.0005

    Allele frequency

    *1=0.53

    Biogeographical group
    More info on groups

    East Asian

    Population description

    Study Cohort: p-value refers to difference in AUC0-24.

    2.

    Study type

    cohort

    Study size

    15

    Association p-value

    = 0.0035

    Allele frequency

    *1=0.53

    Biogeographical group
    More info on groups

    East Asian

    Population description

    Study Cohort: p-value refers to difference in CL/F.

    3.

    Study type

    cohort

    Study size

    15

    Association p-value

    = 0.0052

    Allele frequency

    *1=0.53

    Biogeographical group
    More info on groups

    East Asian

    Population description

    Study Cohort: p-value refers to difference in Cmax.

    4.

    Study type

    cohort

    Study size

    15

    Association p-value

    = 0.3226

    Allele frequency

    *1=0.53

    Biogeographical group
    More info on groups

    East Asian

    Population description

    Study Cohort: p-value refers to difference in t1/2.

    Note: Alleles in PharmGKB are mapped to the positive chromosomal strand. Therefore, variants in genes on the "minus" strand (eg. VKORC1) are complemented in PharmGKB annotations.

    History

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