Post-mortem analysis of suicide victims shows ABCB1 haplotype 1236T–2677T–3435T as a candidate predisposing factor behind adverse drug reactions in females

Background Genetic variation in efflux transporter, permeability glycoprotein (P-gp), has recently been associated with completed violent suicides and also violent suicide attempts. As depression is known to be a risk factor for suicide and many antidepressants are P-gp substrates, it has been speculated that inadequate antidepressant treatment response or adverse side effects could be involved. Objectives The aim of this study was to investigate whether there is an association between the P-gp coding ABCB1 gene and completed suicides in citalopram users. Also, the effect of sex and suicide method used (violent vs. non-violent) was evaluated. Materials and methods All cases included in the study population, 349 completed suicide victims and 284 controls, were shown to be positive for antidepressant citalopram in a post-mortem toxicological drug screen. ABCB1 1236C>T, 2677G/A>T, and 3435C>T polymorphisms were determined by TaqMan genotyping assays. Haplotypes were constructed from genotype data using the PHASE software. The association between the manner of death and the ABCB1 haplotype was tested with logistic regression analysis. Results No statistically significant differences were observed in the ABCB1 allele or genotype frequencies between the suicide and control groups. However, the ABCB1 1236T–2677T–3435T haplotype was associated with completed suicides of female citalopram users (odds ratio: 2.23; 95% confidence interval: 1.22–4.07; P=0.009). After stratification by the method used for suicide, the association emerged in fatal intoxications (odds ratio: 2.51; 95% confidence interval: 1.29–4.87; P=0.007). In other groups, no statistically significant associations were observed. Conclusion Our results suggest that female citalopram users with ABCB1 1236T–2677T–3435T are more vulnerable to adverse effects of the drugs as this haplotype was enriched in non-violent suicides of female citalopram users. Even though the biological mechanism behind this observation is unknown, the results provide another example of the importance of sex-based segregation in pharmacogenetics studies. Correspondence to Anna-Liina Rahikainen, MSc, Department of Forensic Medicine, PO Box 40 (Kytösuontie 11) University of Helsinki, Helsinki FI-00014, Finland Tel: +358 504 151 573; e-mail: anna-liina.rahikainen@helsinki.fi Received November 10, 2017 Accepted January 27, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

from Genetics via xlomafota13 on Inoreader http://ift.tt/2BSOstc
via IFTTT