No ethnic difference between Caucasian and Japanese hepatic samples in the expression frequency of CYP3A5 and CYP3A7 proteins

Biochem Pharmacol. 1999 Apr 15;57(8):935-9. doi: 10.1016/s0006-2952(98)00375-x.

Abstract

Ethnic differences in the pharmacokinetics of nifedipine, a substrate of CYP3A, and in CYP3A7 expression have been reported. The aim of the present study was to measure the protein levels of CYP3A4, CYP3A5, and CYP3A7 and nifedipine oxidation activity in hepatic microsomes from 15 Caucasian and 15 Japanese patients for comparison between the two ethnic groups. Nifedipine oxidation activity and CYP3A4 protein level were well correlated. No significant difference between Caucasian and Japanese microsomal samples was found in nifedipine oxidation activity or in the CYP3A4 protein level. CYP3A5 was detected in 6 of 15 Caucasian samples and in 5 of 15 Japanese samples, but no ethnic difference was found in either the frequency of expression or its protein level. CYP3A7 was found in 10 of 15 Caucasian samples and in 14 of 15 Japanese samples. Although the estimated CYP3A7 protein level was higher in the Japanese than in the Caucasian samples, its protein level was much lower than that of CYP3A4. These results imply that the contribution of CYP3A5 or CYP3A7 to the purported Caucasian-Japanese ethnic difference in the overall CYP3A activity seems to be small.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aryl Hydrocarbon Hydroxylases*
  • Asian Continental Ancestry Group / genetics*
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • European Continental Ancestry Group / genetics*
  • Female
  • Gene Expression
  • Gene Frequency
  • Humans
  • Japan
  • Male
  • Microsomes, Liver / enzymology
  • Middle Aged
  • Nifedipine / metabolism
  • Oxidation-Reduction

Substances

  • Cytochrome P-450 Enzyme System
  • Aryl Hydrocarbon Hydroxylases
  • CYP3A protein, human
  • CYP3A5 protein, human
  • CYP3A7 protein, human
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Nifedipine