4β-Hydroxycholesterol is a new endogenous CYP3A marker: Relationship to CYP3A5 genotype, quinine 3-hydroxylation and sex in Koreans, Swedes and Tanzanians
Pharmacogenetics and Genomics, ISSN: 1744-6872, Vol: 18, Issue: 3, Page: 201-208
2008
- 130Citations
- 36Captures
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Metrics Details
- Citations130
- Citation Indexes130
- 130
- CrossRef111
- Captures36
- Readers36
- 36
Article Description
OBJECTIVES: To study the potential endogenous marker of CYP3A activity, 4β-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 4β-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 4β-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 4β- 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 4β-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 4β- 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 4β-hydroxycholesterol may be used as an endogenous marker of CYP3A activity (CYP3A4+5). © 2008 Lippincott Williams & Wilkins, Inc.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=40049103597&origin=inward; http://dx.doi.org/10.1097/fpc.0b013e3282f50ee9; http://www.ncbi.nlm.nih.gov/pubmed/18300941; https://journals.lww.com/01213011-200803000-00004; https://dx.doi.org/10.1097/fpc.0b013e3282f50ee9; https://insights.ovid.com/crossref?an=01213011-200803000-00004
Ovid Technologies (Wolters Kluwer Health)
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