Related Experiment Video
Updated: May 31, 2026

Reverse Genetics to Engineer Positive-Sense RNA Virus Variants
Published on: June 9, 2022
Novel cytochrome P450-2D6 promoter sequence variations in hepatitis C positive and negative subjects
Martin T Ho1, Edward J Kelly, Miklos Bodor
1Department of Pharmaceutics, University of Washington, Seattle, WA 98195-7610, USA.
Introduction:
CYP2D6 is a liver enzyme that metabolizes more that 25% of drugs and thus may play a pivotal role in drug-drug interactions. The promoter sequences of cytochrome P450 2D6 (CYP2D6) gene could impact metabolic activity.
Methods:
We analyzed genetic variations in the promoter sequence of CYP2D6 gene for 71 hepatitis C negative and 15 hepatitis C positive subjects.
Results:
We found two novel genetic variants -1822A→G; -1740C→T, only in two patients with hepatitis C. Also, two linked new promoter sequence variations at -2060 G→A and -2053 T→G nucleotide positions that present in both hepatitis C negative and positive subjects are identified. The -2060 and -2053 variations are confirmed to be in linkage disequilibrium. The individuals with -2060A/A, and -2053G/G variation appeared to be associated with significantly lower levels of liver CYP2D6 mRNA. Analysis of CYP2D6 enzymatic activity in *1/*1 (wild type) subjects revealed that hepatitis C positive subjects expressed about 2.6-fold lower activity (24.0 ± 1.5 vs. 62.6 ± 3.7 pmol/min/mg; p = 0.0061) relative to hepatitis C negative.
Conclusion:
These data suggest that promoter variations -1822A→G and -1740C→T are present only in hepatitis C infected subjects. Hepatitis C positive individuals were associated with a lower liver CYP2D6 enzyme activity.
Related Concept Videos
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes
Hepatitis
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters
Principles of Pharmacogenetics: Types of Genetic Variants
Comparing Copy Number Variations and SNPs
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...

