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Updated: Jun 20, 2026

A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene
Published on: April 1, 2019
Candidate-gene-based study of CYP3A-related single-nucleotide polymorphisms using 4β-hydroxycholesterol/cholesterol
Ryota Tanaka1, Yosuke Suzuki2, Teruhide Koyama3,4
1Department of Clinical Pharmacy, Oita University Hospital, 1-1 Idaigaoka, Hasama, Yufu, Oita, 879-5593, Japan. rtanaka@oita-u.ac.jp.
Purpose:
CYP3A4 and CYP3A5 are major drug‑metabolizing enzymes that require electrons supplied by P450 oxidoreductase (POR) for catalytic cycle. CYP3A expression is regulated by the nuclear receptors; constitutive androstane receptor (CAR) and pregnane X receptor (PXR). Single-nucleotide polymorphisms (SNPs) of CYP3A5, CYP3A4, POR, CAR, and PXR have been documented to modulate CYP3A enzyme activity and/or expression. We performed a targeted candidate-gene-based analysis of selected CYP3A-related SNPs associated with variability in CYP3A activity in a relatively large sample of general Japanese population.
Methods:
The study population was sampled from the general population participating in the J-MICC Study, and comprised 351 adults who underwent health checkups at Kyoto Prefectural University of Medicine, with genotyping of one SNP in CYP3A5, one SNP in CYP3A4, one SNP in POR, two SNPs in CAR, and six SNPs in PXR. 4β-hydroxycholesterol (4β-OHC) was used as endogenous biomarker of CYP3A activity. Plasma 4β-OHC levels were measured using ultra-high-performance liquid chromatography coupled to tandem mass spectrometry, and normalized to total cholesterol (TC).
Results:
In univariate analyses, CYP3A5 expressors (*1/*1, *1/*3) exhibited approximately 25% higher median 4β-OHC/TC ratio than non-expressors (*3/*3) (p < 0.001). Carriers of the rs2242480 variant and POR*28 showed significantly higher 4β-OHC/TC ratios than their respective non-carriers (p < 0.001 and p = 0.044, respectively), whereas no significant differences were observed for CAR or PXR SNPs. Multiple linear regression analysis with demographic and clinical covariates as independent variables identified CYP3A5*3 and sex as independent predictors of 4β-OHC/TC ratio.
Conclusion:
These findings suggest that when assessing CYP3A activity using 4β-OHC/TC ratio as biomarker, only the CYP3A5*3 genotype may need to be considered.
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