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

Pharmacogenomics J. 2018 Jan;18(1):121-126. doi: 10.1038/tpj.2016.74. Epub 2016 Nov 29.

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.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Adolescent
  • Adult
  • Antipsychotic Agents / therapeutic use
  • Black or African American / genetics*
  • Blood-Brain Barrier / metabolism
  • Body Mass Index
  • Brain / drug effects
  • Brain / metabolism*
  • DNA Methylation / drug effects
  • DNA Methylation / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Obesity / genetics
  • Polymorphism, Genetic / genetics
  • Weight Gain / drug effects
  • Weight Gain / genetics
  • White People / genetics*
  • Young Adult

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antipsychotic Agents