Selected ABCB1 Single Nucleotide Polymorphisms and its Haplotype – Connection with Development of Depression and Treatment Efficacy

The aim was to evaluate the impact of ABCB1 polymorphisms, C1236T and G2677T/A on the incidence of depression, its progression and effectiveness of antidepressant treatment in Polish population. Analyses were performed in 92 patients with recurrent depressive disorder (rDD) using automated sequencing. The obtained data were correlated with the results for C3435T polymorphism published earlier. Following that, a haplotype analysis was performed. For G2677T/A, the severity of depressive symptoms was higher among patients with GG. The more severe course of disease, the more frequently the lack of A or T allele was observed. Moreover, better effectiveness of the therapy was indicated in individuals with 1236 CC as well as in 2677 GG. Additionally, association of C1236T and (C1236T-G2677T/A-C3435T) haplotype with depression development was observed. Simultaneously, G2677T/A was connected with the severity of depressive symptoms. Both of the examined polymorphisms have influence on the effectiveness of antidepressant medications. Address for correspondence: Dr. Agnieszka Maria Jeleñ ORCID number: 0000-0002-3565-7075 Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland Tel/Fax: +48 42 677 91 28 E-mail: agnieszka.jelen@umed.lodz. pl INTRODUCTION Depression is one of the commonest and widespread diseases. It is now estimated that the number of adults with depressive disorders in Polish population is over one million (EZOP-Polska 2012). One of the types of depression is rDD which is described as the tendency of an individual to recur depressive episodes with intervals with lack of depression symptoms. Despite the high prevalence of depression, researchers still know too little about the pathogenesis of this illness. There are certain risk factors which may predispose to depression development: gender, economic disadvantages, educational level or co-existing chronic illnesses. However, it is sometimes difficult to determine whether depression is a cause or a consequence of different diseases. Suggested causes also include hereditary factors. People who have someone with depression in their immediate family, run a much higher risk to develop this disease (Sullivan et al. 2000). It has been recently suggested that polymorphisms of ABCB1, especially single nucleotide polymorphism (SNP) C3435T, may be associated with prevalence of depression (Fujii et al. 2012; Ozbey et al. 2014). The researchers’ previously published results confirmed this hypothesis (Jeleñ et al. 2015). In addition, it has been suggested that other common SNPs (for example, C1236T, G2677T/A) and several haplotypes created by the above mentioned ABCB1 SNPs are associated with the development of depression (Xie et al. 2015). Each of these SNPs occurs with a high prevalence in Caucasian population, thus presumptive medical consequences of their presence may concern a significant number of peoInt J Hum Genet, 19(1): 1-11 (2019) DOI: 10.31901/24566330.2019/19.01. 672 © Kamla-Raj 2019 PRINT: ISSN 0972-3757 ONLINE: ISSN 2456-6330 2 AGNIESZKA MARIA JELEÑ, ALEKSANDRA SALAGACKA-KUBIAK, KAROLINA ROPICKA ET AL. ple. There is a possible link between these SNPs and the gene expression, function and the amount of active P-glycoprotein (P-gp), encoded by ABCB1 (Hitzl et al. 2004; Shou et al. 2012). Moreover, physiological localization (for example, intestine, liver, kidneys, blood-brain or blood-placenta barrier), the main function (protection the cells of the body from toxic xenobiotics) and substrate specificity of P-gp (for example, anticancer drugs, β-blockers, antibiotics, steroids, antiarrhythmics and antidepressants) suggest its influence on bioavailability as well as effect of most popular drugs. The relation between neurological side effects (Ozbey et al. 2017), suicides (Rahikainen et al. 2018) or the effectiveness of certain medicines (Wolking et al. 2015), particularly SSRIs (Amare et al. 2017), and the selected ABCB1 polymorphisms was shown. Also, in the researchers’ aforementioned study, the association between C3435T and the efficacy of the therapy were indicated (Jeleñ et al. 2015). Nevertheless, the issue of this relationship remains inconsistent, while ABCB1 seems to be an important candidate gene in creating a model of personalized psychiatry (Amare et al. 2017).