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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 CYP3A5 genotypes on CYP3A enzymes activity using the plasma 4β-hydroxycholesterol (4β-OHC)/cholesterol (Chol) ratio, a kn...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9739497/ https://www.ncbi.nlm.nih.gov/pubmed/36499500 http://dx.doi.org/10.3390/ijms232315168 |
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author | Mlugu, Eulambius M. Minzi, Omary M. Kamuhabwa, Appolinary A. R. Diczfalusy, Ulf Aklillu, Eleni |
author_facet | Mlugu, Eulambius M. Minzi, Omary M. Kamuhabwa, Appolinary A. R. Diczfalusy, Ulf Aklillu, Eleni |
author_sort | Mlugu, Eulambius M. |
collection | PubMed |
description | 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 CYP3A5 genotypes on CYP3A enzymes activity using the plasma 4β-hydroxycholesterol (4β-OHC)/cholesterol (Chol) ratio, a known endogenous biomarker. Tanzanian pregnant women (n = 110) and non-pregnant women (n = 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 CYP3A5 (*3, *6, *7) 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 CYP3A5 genotypes on the 4β-OHC/Chol ratio in pregnant women. No significant effect of the pregnancy status or the CYP3A5 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 (p = 0.02). Pregnant women had a significantly higher mean 4β-OHC/Chol ratio than non-pregnant women, (p < 0.001). In non-pregnant women, the mean 4β-OHC/Chol ratio was significantly lower in carriers of defective CYP3A5 alleles (*3, *6 or *7) as compared to women with the CYP3A5*1/*1 genotypes (p = 0.002). Pregnancy increases CYP3A enzymes activity in a gestational-stage manner. The CYP3A5 genotype predicts CYP3A enzymes activity in the black Tanzanian population, but not during pregnancy-mediated CYP3A enzyme induction. |
format | Online Article Text |
id | pubmed-9739497 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97394972022-12-11 Pregnancy Increases CYP3A Enzymes Activity as Measured by the 4β-Hydroxycholesterol/Cholesterol Ratio Mlugu, Eulambius M. Minzi, Omary M. Kamuhabwa, Appolinary A. R. Diczfalusy, Ulf Aklillu, Eleni Int J Mol Sci Article 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 CYP3A5 genotypes on CYP3A enzymes activity using the plasma 4β-hydroxycholesterol (4β-OHC)/cholesterol (Chol) ratio, a known endogenous biomarker. Tanzanian pregnant women (n = 110) and non-pregnant women (n = 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 CYP3A5 (*3, *6, *7) 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 CYP3A5 genotypes on the 4β-OHC/Chol ratio in pregnant women. No significant effect of the pregnancy status or the CYP3A5 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 (p = 0.02). Pregnant women had a significantly higher mean 4β-OHC/Chol ratio than non-pregnant women, (p < 0.001). In non-pregnant women, the mean 4β-OHC/Chol ratio was significantly lower in carriers of defective CYP3A5 alleles (*3, *6 or *7) as compared to women with the CYP3A5*1/*1 genotypes (p = 0.002). Pregnancy increases CYP3A enzymes activity in a gestational-stage manner. The CYP3A5 genotype predicts CYP3A enzymes activity in the black Tanzanian population, but not during pregnancy-mediated CYP3A enzyme induction. MDPI 2022-12-02 /pmc/articles/PMC9739497/ /pubmed/36499500 http://dx.doi.org/10.3390/ijms232315168 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Mlugu, Eulambius M. Minzi, Omary M. Kamuhabwa, Appolinary A. R. Diczfalusy, Ulf Aklillu, Eleni Pregnancy Increases CYP3A Enzymes Activity as Measured by the 4β-Hydroxycholesterol/Cholesterol Ratio |
title | Pregnancy Increases CYP3A Enzymes Activity as Measured by the 4β-Hydroxycholesterol/Cholesterol Ratio |
title_full | Pregnancy Increases CYP3A Enzymes Activity as Measured by the 4β-Hydroxycholesterol/Cholesterol Ratio |
title_fullStr | Pregnancy Increases CYP3A Enzymes Activity as Measured by the 4β-Hydroxycholesterol/Cholesterol Ratio |
title_full_unstemmed | Pregnancy Increases CYP3A Enzymes Activity as Measured by the 4β-Hydroxycholesterol/Cholesterol Ratio |
title_short | Pregnancy Increases CYP3A Enzymes Activity as Measured by the 4β-Hydroxycholesterol/Cholesterol Ratio |
title_sort | pregnancy increases cyp3a enzymes activity as measured by the 4β-hydroxycholesterol/cholesterol ratio |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9739497/ https://www.ncbi.nlm.nih.gov/pubmed/36499500 http://dx.doi.org/10.3390/ijms232315168 |
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