Pregnancy Increases CYP3A Enzymes Activity as Measured by the 4β-Hydroxycholesterol/Cholesterol Ratio
Changes in cortisol and other hormones during pregnancy may alter CYP3A enzymes activity, but data from sub-Saharan Africa are sparse. We investigated the effect of pregnancy and <i>CYP3A5</i> genotypes on CYP3A enzymes activity using the plasma 4β-hydroxycholesterol (4β-OHC)/cholesterol...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/23/15168 |
| Summary: | Changes in cortisol and other hormones during pregnancy may alter CYP3A enzymes activity, but data from sub-Saharan Africa are sparse. We investigated the effect of pregnancy and <i>CYP3A5</i> genotypes on CYP3A enzymes activity using the plasma 4β-hydroxycholesterol (4β-OHC)/cholesterol (Chol) ratio, a known endogenous biomarker. Tanzanian pregnant women (<i>n</i> = 110) and non-pregnant women (<i>n</i> = 59) controls were enrolled. Plasma 4β-OHC and Chol were determined in the second and third trimesters for pregnant women and once for non-pregnant women using gas chromatography–mass spectrometry. Genotyping for <i>CYP3A5</i> (<i>*3</i>, <i>*6</i>, <i>*7</i>) was performed. Wilcoxon Signed-Rank Test and Mann–Whitney U test were used to compare the median 4β-OHC/Chol ratio between trimesters in pregnant women and between pregnant and non-pregnant women. Repeated-measure ANOVA was used to evaluate the effect of the <i>CYP3A5</i> genotypes on the 4β-OHC/Chol ratio in pregnant women. No significant effect of the pregnancy status or the <i>CYP3A5</i> genotype on the cholesterol level was observed. The plasma 4β-OHC/Chol ratio significantly increased by 7.3% from the second trimester to the third trimester (<i>p</i> = 0.02). Pregnant women had a significantly higher mean 4β-OHC/Chol ratio than non-pregnant women, (<i>p</i> < 0.001). In non-pregnant women, the mean 4β-OHC/Chol ratio was significantly lower in carriers of defective <i>CYP3A5</i> alleles (*3, *6 or *7) as compared to women with the <i>CYP3A5*1/*1</i> genotypes (<i>p</i> = 0.002). Pregnancy increases CYP3A enzymes activity in a gestational-stage manner. The <i>CYP3A5</i> genotype predicts CYP3A enzymes activity in the black Tanzanian population, but not during pregnancy-mediated CYP3A enzyme induction. |
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| ISSN: | 1661-6596 1422-0067 |