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International Journal of Legal Medicine

, Volume 127, Issue 3, pp 579–586 | Cite as

ABCB1 gene polymorphisms are associated with fatal intoxications involving venlafaxine but not citalopram

  • L. Karlsson
  • H. Green
  • A. L. Zackrisson
  • F. Bengtsson
  • I. Jakobsen Falk
  • B. Carlsson
  • J. Ahlner
  • F. C. KugelbergEmail author
Original Article

Abstract

P-glycoprotein (P-gp), encoded by the ABCB1/MDR1 gene, is a drug transporter at the blood–brain barrier. Several polymorphisms in the ABCB1 gene are known to affect the activity and/or expression of P-gp, thereby influencing the treatment response and toxicity of P-gp substrates like citalopram and venlafaxine. In this study, we aimed to investigate the frequency of ABCB1 genotypes in forensic autopsy cases involving these two antidepressants. Further, the distribution of ABCB1 genotypes in deaths related to intoxication was compared to cases not associated to drug intoxication. The study included 228 forensic autopsy cases with different causes and manners of deaths. The ABCB1 single nucleotide polymorphisms (SNPs) G1199A, C1236T, C3435T and G2677T/A for these individuals were determined. The SNPs C1236T and C3435T in venlafaxine-positive cases were significantly different between the intoxication cases and non-intoxications. This was not seen for cases involving citalopram, indicating that the effect of genetic variants might be substrate specific. This novel finding should, however, be confirmed in future studies with larger number of cases.

Keywords

ABCB1 Citalopram Forensic material Genotype Postmortem Venlafaxine 

Notes

Acknowledgments

The authors express their gratitude to Anita Holmgren for assistance with database processing. This original work has been supported by grants from the National Board of Forensic Medicine in Sweden (HG, ALZ, JA, FCK) and the Swedish Research Council (HG, FB, JA, FCK).

Supplementary material

414_2013_849_MOESM1_ESM.doc (250 kb)
Table S 1 (DOC 250 kb)
414_2013_849_MOESM2_ESM.doc (249 kb)
Table S 2 (DOC 249 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • L. Karlsson
    • 1
  • H. Green
    • 1
    • 2
    • 3
  • A. L. Zackrisson
    • 3
  • F. Bengtsson
    • 1
  • I. Jakobsen Falk
    • 1
  • B. Carlsson
    • 1
  • J. Ahlner
    • 1
    • 3
  • F. C. Kugelberg
    • 1
    • 3
    Email author
  1. 1.Division of Drug Research, Clinical Pharmacology, Department of Medical and Health SciencesLinköping UniversityLinköpingSweden
  2. 2.Science for Life Laboratory, School of Biotechnology, Division of Gene TechnologyRoyal Institute of TechnologyStockholmSweden
  3. 3.Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic MedicineLinköpingSweden

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