title: Biological and genetic factors associated with ABCB1 and pregnane-X-receptor expressions in peripheral blood mononuclear cells in the STANISLAS cohort.
abstract: BACKGROUND
  ABCB1 is a membrane transporter ubiquitously expressed particularly in peripheral blood mononuclear cells (PBMCs). Resistance to drugs is associated with genetic variations of its gene and with modulation of its expression through the pregnane-X-receptor (PXR) transcription factor. We have previously shown that ABCB1 polymorphisms were associated with blood lipid concentrations.
  
  
  METHODS
  We wanted to investigate the variation factors and the genetic determinants of ABCB1 and PXR expressions in PBMCs, and their interrelationships with plasma lipid levels. ABCB1 and PXR mRNA were quantified by real-time quantitative RT-PCR in PBMCs of 42 men and 39 women.
  
  
  RESULTS
  ABCB1 and PXR were both expressed in PBMCs of all individuals, but their expressions were not significantly correlated. ABCB1 mRNA was correlated with body mass index (BMI; p=0.01) and age (p=0.03). In women, lymphocyte count also correlated with ABCB1 transcripts (p<0.01). After adjustment for BMI, correlation with age disappears. PXR mRNA expression depends on gender with men expressing higher PXR levels (p=0.01). PXR expression also correlates with γ-glutamyltransferase (GGT; p=0.02), but this disappeared after adjustment.
  
  
  CONCLUSIONS
  Neither ABCB1 nor PXR expressions correlate with ABCB1 gene variants. Finally, association between ABCB1 or PXR expression in PBMCs and lipid or apolipoprotein plasma concentrations were not significant in this subset of healthy subjects. These results should be confirmed in a larger population sample and extended to patients with various cardiovascular risk profiles.
authors: EA 4373 Cardiovascular Genetics, Faculty of Pharmacy, Nancy-Université, Nancy, France.
authors: Elise
authors: E
authors: Jeannesson
authors: Gerard
authors: G
authors: Siest
authors: Bernard
authors: B
authors: Herbeth
authors: Laetitia
authors: L
authors: Albertini
authors: Payman
authors: P
authors: Shahabi
authors: Michele
authors: M
authors: Pfister
authors: Sophie
authors: S
authors: Visvikis-Siest
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000367:Age Factors; D001053:Apolipoproteins / Q000097:blood; D015992:Body Mass Index; D005260:Female; D015870:Gene Expression; D014644:Genetic Variation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008055:Lipids / Q000097:blood*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D000077297:Pregnane X Receptor; D012333:RNA, Messenger / Q000378:metabolism; D011987:Receptors, Steroid / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001053:Apolipoproteins; D008055:Lipids; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D011987:Receptors, Steroid