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.
authors.affiliation: Department of Biomedicine, Health Aarhus University, Aarhus C-DK, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Vendelbo
authors.affiliation: Department of Biomedicine, Health Aarhus University, Aarhus C-DK, Denmark.
authors.forename: R H
authors.initials: RH
authors.lastname: Olesen
authors.affiliation: Department of Biomedicine, Health Aarhus University, Aarhus C-DK, Denmark.
authors.forename: J K
authors.initials: JK
authors.lastname: Lauridsen
authors.affiliation: Department of Biomedicine, Health Aarhus University, Aarhus C-DK, Denmark.|Center for Diabetes Research, Department of Clinical Pharmacology, Copenhagen University Hospital Gentofte and Rigshospitalet, Copenhagen, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Rungby
authors.affiliation: The Lieber Institute for Brain Development, Maltz Research Laboratories, John Hopkins Medical Campus, Baltimore, MD, USA.|Department of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Kleinman
authors.affiliation: The Lieber Institute for Brain Development, Maltz Research Laboratories, John Hopkins Medical Campus, Baltimore, MD, USA.|Department of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Hyde
authors.affiliation: Department of Biomedicine, Health Aarhus University, Aarhus C-DK, Denmark.
authors.forename: A
authors.identifier: 0000-0001-8765-8443
authors.initials: A
authors.lastname: Larsen
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000378:metabolism; D015992:Body Mass Index; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D015430:Weight Gain / Q000187:drug effects / Q000235:genetics; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014150:Antipsychotic Agents