4Beta-hydroxycholesterol is a new endogenous CYP3A marker: relationship to CYP3A5 genotype, quinine 3-hydroxylation and sex in Koreans, Swedes and Tanzanians

Pharmacogenet Genomics. 2008 Mar;18(3):201-8. doi: 10.1097/FPC.0b013e3282f50ee9.


Objectives: To study the potential endogenous marker of CYP3A activity, 4beta-hydroxycholesterol, and its relation to sex and the CYP3A5 geno/haplotypes and compare with CYP3A4/5 catalyzed 3-hydroxylation of quinine in the three major races.

Methods: The plasma concentration of 4beta-hydroxycholesterol was measured in healthy Tanzanians (n=138), Swedes (n=161) and Koreans (n=149) by gas chromatography-mass spectrometry. The metabolic ratio of quinine/3-hydroxyquinine in plasma 16-h post dose was determined by high performance liquid chromatography, previously reported in Tanzanians and Swedes, and now also in Koreans. The participants were genotyped for relevant alleles of CYP3A5.

Results: The mean plasma concentrations of 4beta-hydroxycholesterol in Koreans, Swedes and Tanzanians were 29.3, 26.8 and 21.9 ng/ml, respectively (P<0.01 between all three populations). Within all three populations there were significant differences in 4beta-hydroxycholesterol levels between the CYP3A5 genotypes. Women had higher concentrations than men, but the difference was only significant in Tanzanians (P<0.001) and Koreans (P<0.00001). The quinine/3-hydroxyquinine metabolic ratio was significantly different in all three populations with the highest CYP3A activity in Koreans and the lowest in Tanzanians. Korean women had a lower metabolic ratio than men (P<0.00001). Significant correlations between 4beta-hydroxycholesterol and quinine 3-hydroxylation were found in Tanzanians and Koreans.

Conclusion: Clear differences in the activity of both CYP3A4 and CYP3A5 were shown in the three major human races. Both 4beta-hydroxycholesterol and quinine/3-hydroxyquinine metabolic ratio showed a higher CYP3A activity in women than in men. The results give strong evidence that the plasma concentration of 4beta-hydroxycholesterol may be used as an endogenous marker of CYP3A activity (CYP3A4+5).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Asian People / genetics
  • Biomarkers / blood
  • Black People / genetics
  • Cytochrome P-450 CYP3A / genetics*
  • Cytochrome P-450 CYP3A / metabolism
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Hydroxycholesterols / blood*
  • Hydroxylation
  • Korea
  • Male
  • Pharmacogenetics
  • Quinine / metabolism*
  • Sex Characteristics
  • Sweden
  • Tanzania
  • White People / genetics


  • Biomarkers
  • Hydroxycholesterols
  • cholest-5-ene-3,4-diol
  • Quinine
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human