Increasing BMI is associated with reduced expression of P-glycoprotein (ABCB1 gene) in the human brain with a stronger association in African Americans than Caucasians

J. Vendelbo, R. H. Olesen, J. K. Lauridsen, J. Rungby, Joel Kleinman, Thomas Hyde, A. Larsen

Research output: Contribution to journalArticle

Abstract

The efflux pump, p-glycoprotein, controls bioavailability and excretion of pharmaceutical compounds. In the blood–brain barrier, p-glycoprotein regulates the delivery of pharmaceutical substances to the brain, influencing efficacy and side effects for some drugs notably antipsychotics. Common side effects to antipsychotics include obesity and metabolic disease. Polymorphisms in the ABCB1 gene coding for p-glycoprotein are associated with more severe side effects to neuro-pharmaceuticals as well as weight gain, indicating a potential link between p-glycoprotein function and metabolic regulation. Using microarray data analysis from 145 neurologically sound adults, this study investigated the association between body mass index (BMI) and ABCB1 expression in the frontal cortex. Increasing BMI values were associated with a statistically significantly reduced expression of ABCB1. Investigation of DNA methylation patterns in a subgroup of 52 individuals found that the methylation/expression ratios of ABCB1 were unaffected by increasing BMI values. Interestingly, the effect of BMI on ABCB1 expression appeared stronger in African Americans than in Caucasians.The Pharmacogenomics Journal advance online publication, 29 November 2016; doi:10.1038/tpj.2016.74.

Original languageEnglish (US)
JournalPharmacogenomics Journal
DOIs
StateAccepted/In press - Nov 29 2016

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P-Glycoprotein
African Americans
Glycoproteins
Body Mass Index
Brain
Antipsychotic Agents
Genes
Pharmaceutical Preparations
Pharmacogenetics
Metabolic Diseases
Frontal Lobe
DNA Methylation
Microarray Analysis
Drug-Related Side Effects and Adverse Reactions
Methylation
Biological Availability
Weight Gain
Publications
Obesity

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

Cite this

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title = "Increasing BMI is associated with reduced expression of P-glycoprotein (ABCB1 gene) in the human brain with a stronger association in African Americans than Caucasians",
abstract = "The efflux pump, p-glycoprotein, controls bioavailability and excretion of pharmaceutical compounds. In the blood–brain barrier, p-glycoprotein regulates the delivery of pharmaceutical substances to the brain, influencing efficacy and side effects for some drugs notably antipsychotics. Common side effects to antipsychotics include obesity and metabolic disease. Polymorphisms in the ABCB1 gene coding for p-glycoprotein are associated with more severe side effects to neuro-pharmaceuticals as well as weight gain, indicating a potential link between p-glycoprotein function and metabolic regulation. Using microarray data analysis from 145 neurologically sound adults, this study investigated the association between body mass index (BMI) and ABCB1 expression in the frontal cortex. Increasing BMI values were associated with a statistically significantly reduced expression of ABCB1. Investigation of DNA methylation patterns in a subgroup of 52 individuals found that the methylation/expression ratios of ABCB1 were unaffected by increasing BMI values. Interestingly, the effect of BMI on ABCB1 expression appeared stronger in African Americans than in Caucasians.The Pharmacogenomics Journal advance online publication, 29 November 2016; doi:10.1038/tpj.2016.74.",
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AU - Larsen, A.

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