ArticleClinical and translational science2024
Evaluation of the usefulness of plasma 4β-hydroxycholesterol concentration normalized by 4α-hydroxycholesterol for accurate CYP3A phenotyping.
Article in Clinical and translational science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 3 citations in OpenAlex.
- Candidate-gene-based study of CYP3A-related single-nucleotide polymorphisms using 4β-hydroxycholesterol/cholesterol ratio as biomarker in a Japanese cohort.European journal of clinical pharmacology · 2026Article
- Impact of Complex Genetic and Drug-Drug Interactions on Tamoxifen Metabolism and Efficacy.Journal of personalized medicine · 2025Review
- Evaluation of the usefulness of plasma 4β-hydroxycholesterol concentration normalized by 4α-hydroxycholesterol for accurate CYP3A phenotyping.Clinical and translational science · 2024Article
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Authors and funding
15 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plasma 4β-hydroxycholesterol (OHC) has drawn attention as an endogenous substrate indicating CYP3A activity. Plasma 4β-OHC is produced by hydroxylation by CYP3A4 and CYP3A5 and by cholesterol autoxidation. Plasma 4α-OHC is produced by cholesterol autoxidation and not affected by CYP3A activity. This study aimed to evaluate the usefulness of plasma 4β-OHC concentration minus plasma 4α-OHC concentration (4β-OHC-4α-OHC) compared with plasma 4β-OHC concentration and 4β-OHC/total cholesterol (TC) ratio in cross-sectional evaluation of CYP3A activity. Four hundred sixteen general adults were divided into 191 CYP3A5*1 carriers and 225 non-carriers. Twenty-six patients with chronic kidney disease (CKD) with CYP3A5*1 allele were divided into 14 with CKD stage 3 and 12 with stage 4-5D. Area under the receiver operating characteristic curve (AUC) for the three indices were evaluated for predicting presence or absence of CYP3A5*1 allele in general adults, and for predicting CKD stage 3 or stage 4-5D in patients with CKD. There was no significant difference between AUC of 4β-OHC-4α-OHC and AUC of plasma 4β-OHC concentration in general adults and in patients with CKD. AUC of 4β-OHC-4α-OHC was significantly smaller than that of 4β-OHC/TC ratio in general adults (p = 0.025), but the two indices did not differ in patients with CKD. In conclusion, in the present cross-sectional evaluation of CYP3A activity in general adults and in patients with CKD with CYP3A5*1 allele, the usefulness of 4β-OHC-4α-OHC was not different from plasma 4β-OHC concentration or 4β-OHC/TC ratio. However, because of the limitations in study design and subject selection of this research, these findings require verification in further studies.
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