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ABCB1 gene polymorphisms are associated with fatal intoxications involving venlafaxine but not citalopram
KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
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2013 (English)In: International journal of legal medicine (Print), ISSN 0937-9827, E-ISSN 1437-1596, Vol. 127, no 3, 579-586 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2013. Vol. 127, no 3, 579-586 p.
Keyword [en]
ABCB1, Citalopram, Forensic material, Genotype, Postmortem, Venlafaxine
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:kth:diva-123112DOI: 10.1007/s00414-013-0849-0ISI: 000318247100006Scopus ID: 2-s2.0-84877873187OAI: oai:DiVA.org:kth-123112DiVA: diva2:624895
Funder
Swedish Research CouncilScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20130603

Available from: 2013-06-03 Created: 2013-06-03 Last updated: 2017-12-06Bibliographically approved

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CiteExportLink to record
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