Are there factors modifying the expression of enzymes of drug metabolism in obese subjects?

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Journal Title, Volume, Page: 
Fundamental & Clinical Pharmacology 2012, 26: 85-85.
Year of Publication: 
2012
Authors: 
Dr. Célia LLORET-LINARES
Assistance Publique-Hôpitaux de Paris, Université Paris VII, Service de Médecine Interne A, Unité de recherche thérapeutique-Hôpital Lariboisière-75475 Paris Cedex 10; Université Paris Cité-Descartes, Faculté de pharmacie, Unité INSERM U705, CNRS UMR 7157
Dr. Nicolas VEYRIE
Hôpital Ambroise Paré, Chirurgie générale, digestice et métabolique, Université Versailles Saint-Quentin, Assistance Publique-Hôpitaux de Paris, Boulogne-Billancourt 92100
Pr. Jean-Luc BOUILLOT
Hôpital Ambroise Paré, Chirurgie générale, digestice et métabolique, Université Versailles Saint-Quentin, Assistance Publique-Hôpitaux de Paris, Boulogne-Billancourt 92100
Ramzi SHAWAHNA
Université Paris Cité-Descartes, Faculté de pharmacie, Unité INSERM U705, CNRS UMR 7157, 75006-Paris
Current Affiliation: 
Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
Mme Katell PEOCH
Hôpital Ambroise Paré, Chirurgie générale, digestice et métabolique, Université Versailles Saint-Quentin, Assistance Publique-Hôpitaux de Paris, Boulogne-Billancourt 92100
Dr. Christine POITOU
Assistance Publique-Hôpitaux de Paris, Université Paris VI, Service de Nutrition, Hôpital de la Pitié-Salpétrière,75013-Paris
Pr. Stéphane MOULY
Assistance Publique-Hôpitaux de Paris, Université Paris VII, Service de Médecine Interne A, Unité de recherche thérapeutique-Hôpital Lariboisière-75475 Paris Cedex 10; Université Paris Cité-Descartes, Faculté de pharmacie, Unité INSERM U705, CNRS UMR 7157
Pr. Jean-François BERGMANN
Assistance Publique-Hôpitaux de Paris, Université Paris VII, Service de Médecine Interne A, Unité de recherche thérapeutique-Hôpital Lariboisière-75475 Paris Cedex 10; Université Paris Cité-Descartes, Faculté de pharmacie, Unité INSERM U705, CNRS UMR 7157
Pr. Xavier DECLÈVESc
Université Paris Cité-Descartes, Faculté de pharmacie, Unité INSERM U705, CNRS UMR 7157, 75006-Paris
Preferred Abstract (Original): 

Objectives: To describe, in morbid obese subjects, the jejunal expression of efflux transporters and metabolizing enzymes, that the intestinal microbiota and the low-grade inflammation may change.
Methods: The subjects were non-diabetic obese patients (BMI> 35kg / m²). A fragment of jejunal epithelium located about 40cm after the gastroduodenal junction and considered as a surgical waste was preserved during gastric bypass surgery and frozen at -80 ° C. The expressions of genes encoding the transporters: ABCB1/MDR1ABCC2/MRP2, and ABCC3/MRP3; in addition to the enzymes: CYP3A4 and UGT2B7 were analyzed by qRT-PCR. Patients were genotyped for the ABCB1 C3435T polymorphism.
Results: The intestinal epithelium of 28 obese subjects (23 women and 5 men) were analyzed. This population, with a mean age of 40 ± 9.9 years, had a mean BMI of 44.6 ± 5.9kg m². Of those, 10.7% were smokers, 32.1% were hypertensive and 28.6% had a treated sleep apnea syndrome. No chronic treatment of the patients was known to induce transporters and enzymes expression.
qRT-PCR showed that ABCB1/MDR1 was the mainly expressed (84.1 ± 48.8) gene, followed by CYP3A4 (43.2 ± 19.9),ABCC2/MRP2 (22.7 ± 23.3), UGT2B7 (14.5 ± 7.4) and ABCC3/MRP3 (2.0 ± 1.2). A difference between sex in the expression of ABCB1 was at the limit of significativity (136.6 ± 75.3 in men versus 72.7 ± 33.7 in women, p = 0.055). Patients homozygous for the T allele of the gene ABCB1/MDR1 expressed significantly more ABCB1/MDR1 than subjects heterozygous CT and homozygous CC (123.2 ± 59.5 versus 63.5 ± 23.7 and 60.7 ± 22.8 respectively). A correlation between the expression ofABCB1/MDR1 and weight, fat mass, truncal fat mass, BMI, liver enzymes (AST, ALT, GGT) disappeared after adjusting for sex. Similarly, there was no correlation between the markers of inflammation and the gene expression. There was a strong correlation between the expression of each gene.
Conclusion: In obese subjects, inflammation and body composition do not influence jejunal expression of the genes studied. Carriers of the C allele of the gene ABCB1/MDR1 encoding P-gp express significantly less ABCB1/MDR1 gene transcripts than the others.