Genotype of CYP3AP1 associated with CYP3A activity in Chinese Han population

Acta Pharmacol Sin. 2002 Jun;23(6):567-72.

Abstract

Aim: To investigate the distribution of genotype of CYP3AP1 in Chinese Han population and the correlation with CYP3A activity.

Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was employed in CYP3AP1 genotype analysis; using midazolam as probe drug, CYP3A activity of 191 Chinese healthy subjects was measured by plasma 1'-hydroxymidazolam/midazolam (1'-OH-MDZ/MDZ) ratio at 1 h after oral administration of 7.5 mg midazolam.

Results: There was significant difference of CYP3A activity in different genotypes of CYP3AP1 in vivo (P <0.05). The activity of CYP3A in homozygous A(-44) (CYP3AP1*3/CYP3AP1*3) is lower than heterozygous A(-44)G (CYP3AP1*1/CYP3AP1*3), and the CYP3A activity in homozygous G(-44) (CYP3AP1*1/CYP3AP1*1) is t he highest.

Conclusion: There was association between the genotype of CYP3AP1 and increased activity of CYP3A in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aryl Hydrocarbon Hydroxylases / metabolism*
  • Asian People / genetics
  • Cytochrome P-450 CYP3A
  • Ethnicity
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Male
  • Midazolam / blood*
  • Midazolam / metabolism
  • Oxidoreductases, N-Demethylating / metabolism*
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length

Substances

  • Aryl Hydrocarbon Hydroxylases
  • Cyp3a23-3a1 protein, rat
  • Cytochrome P-450 CYP3A
  • Oxidoreductases, N-Demethylating
  • Midazolam