Novel cytochrome P450-2D6 promoter sequence variations in hepatitis C positive and negative subjects.

ABSTRACT: 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.

SUBMITTER: Ho MT 

PROVIDER: S-EPMC3551345 | biostudies-literature | 2011 Jul-Sep

REPOSITORIES: biostudies-literature