Association of MDR1 C3435T polymorphism with bipolar disorder in patients treated with valproic acid

Mol Biol Rep. 2009 Mar;36(3):495-9. doi: 10.1007/s11033-007-9206-z. Epub 2007 Dec 30.

Abstract

P-glycoprotein (P-gp), an efflux transporter protein, is an ABC transporter encoded by the multidrug resistance 1 gene (MDR1, ABCB1). The common synonymous C3435T polymorphism in exon 26 is reported to associate with lower P-gp functional expression and drug uptake. Many extended pharmacogenomics, functional, and complex disease association studies focused mainly on this polymorphism. We investigated the association of exon 26 C3435T genetic variants of MDR1 gene with susceptibility to bipolar disorder and serum valproic acid concentration. Totally, 104 patients meeting DSM-IV criteria for bipolar disorder and 169 controls were admitted to the study. There was statistically significant difference between the genotypes of bipolar patients (CT 91.2%, TT 6.8%, and CC 2%) and controls (CT 52.7%, TT 26%, CC 21.3%) although their allelic distribution was similar. The serum valproic acid concentrations of the patients with CT, TT and CC genotypes were 72.92 +/- 20.55, 80.47 +/- 14.01 and 68.29 +/- 12.17 microg/ml, respectively, and there was no significant difference between the C3435T genotypes.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Adolescent
  • Adult
  • Aged
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / genetics*
  • Bipolar Disorder / metabolism
  • Cytosine / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Valproic Acid / therapeutic use*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Valproic Acid
  • Cytosine