Sorted By Test Name - Mayo Medical Laboratories

3A4O
61242
individual is homozygous (TT) for the CYP3A4*22 (c.522-191C->T) allele. This genotype predicts lower
enzyme activity. Individuals with this genotype may require significantly lower statin doses.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Evans WE, Relling RV: Pharmacogenomics: translating functional
genomics into rational therapeutics. Science 1999;486:487-491 2. Lamda JK, Lin YS, Schuetz EG,
Thummel KE: Genetic contribution to variable human CYP3A-mediated metabolism. Adv Drug Deliv
Rev 2002;18:1271-1294 3. Wang D, Guo Y, Wrighton SA, et al: Intronic polymorphism in CYP3A4
affects hepatic expression and response to statin drugs. Pharmacogenomics J 2011;11:274-286 4. Elens L,
Becker ML, Haufroid V, et al: Novel CYP3A4 intron 6 single nucleotide polymorphism is associated with
simvastatin-mediated cholesterol reduction in the Rotterdam study. Pharmacogenet Genomics
2011;21(12):861-866 5. Elens L, Van Schaik RH, Panin N, et al: Effect of a new functional CYP3A4
polymorphism on calcineurin inhibitor†dose requirements and trough blood levels in stable renal
transplant patients. Pharmacogenomics 2011;12(10):1383-1396
Cytochrome P450 3A4 Genotype, Saliva
Clinical Information: The cytochrome P450 (CYP) 3A4 enzyme is responsible for the metabolism of
approximately 50% of drugs that undergo hepatic metabolism and first pass metabolism in intestinal
epithelial cells, including lipid-lowering drugs. The CYP3A4 enzyme activity is highly variable.(1) While
polymorphisms and mutations have been described for the CYP3A4 gene, they do not explain the highly
variable enzymatic activity of the encoded protein.(2) A CYP3A4 (c522-191C->T) intron 6
polymorphism (CYP3A4*22) affects hepatic expression of CYP3A4 and response to statin drugs. The
CYP3A4*22 allele is associated with reduced CYP3A4 activity, resulting in a better response to
lipid-lowering drugs, such as simvastatin, atorvastatin, or lovastatin. Studies show that CYP3A4 mRNA
level and enzyme activity in the liver with CC genotype were 1.7- and 2.5-fold greater than in CT and TT
carriers, respectively. In 235 patients taking stable doses of drugs for lipid control, carriers of the T allele
required significantly lower statin doses for optimal lipid control than did non-T carriers.(3) These results
indicate that CYP3A4*22 markedly affects expression of CYP3A4 and could serve as a biomarker for
CYP3A4 metabolizer phenotype. The reported allele frequency of CYP3A4*22 in Caucasians was 5% to
8%. The allele frequency is 4.3% in African Americans and in Chinese.
Useful For: As an aid to clinicians in determining therapeutic strategies for drugs that are metabolized
by CYP3A4, including atorvastatin, simvastatin and lovastatin
Interpretation: CC Detected: The CYP3A4 *22 (c.522-191C->T) allele was not identified (ie, CC
genotype detected) in this individual. This genotype predicts higher CYP3A4 enzyme activity. Individuals
with this genotype may require higher statin doses for optimal therapy. CT Detected: This individual is
heterozygous (CT) for the CYP3A4*22 (c.522-191C->T) allele. This genotype predicts lower CYP3A4
enzyme activity. Individuals with this genotype may require lower statin doses. TT Detected: This
individual is homozygous (TT) for the CYP3A4*22 (c.522-191C->T) allele. This genotype predicts lower
enzyme activity. Individuals with this genotype may require significantly lower statin doses.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Evans WE, Relling RV: Pharmacogenomics: translating functional
genomics into rational therapeutics. Science 1999;486:487-491 2. Lamda JK, Lin YS, Schuetz EG,
Thummel KE: Genetic contribution to variable human CYP3A-mediated metabolism. Adv Drug Deliv
Rev 2002;18:1271-1294 3. Wang D, Guo Y, Wrighton SA, et al: Intronic polymorphism in CYP3A4
affects hepatic expression and response to statin drugs. Pharmacogenomics J 2011;11:274-286 4. Elens L,
Becker ML, Haufroid V, et al: Novel CYP3A4 intron 6 single nucleotide polymorphism is associated with
simvastatin-mediated cholesterol reduction in the Rotterdam study. Pharmacogenet Genomics
2011;21(12):861-866 5. Elens L, Van Schaik RH, Panin N, et al: Effect of a new functional CYP3A4
polymorphism on calcineurin inhibitor†dose requirements and trough blood levels in stable renal
transplant patients. Pharmacogenomics 2011;12(10):1383-1396
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