rs2235015 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein (P-glycoprotein - Pgp) that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and their efficacy or potential for adverse side effects. Clinical studies on antidepressant drug dosage, plasma medication levels and treatment outcome suggest monotonic associations for tricyclic antidepressant drugs [PMID 3881999] and threshold models or higher order relationships for selective serotonin reuptake inhibitors [PMID 28648553] and newer antidepressant drugs [PMID 25188033],[PMID 30611837]. However, the link between the increased brain concentrations of antidepressants and a clinically significant response is still to be confirmed. According to a recent review [PMID 27918249], ten studies reported that ABCB1 SNPs have clinical effect on depression outcome and eight - that they do not. However those 18 studies are difficult to compare because they vary within their study design concerning following factors: population (ethnicity, psychiatric condition), tested SNPs, tested antidepressants (Pgp substrates and Pgp non-substrates) and doses, inclusion of drug metabolism monitoring and statistical correction for multiple testing.
A study of ~400 of German psychiatric inpatients with depression conducted in 2007 by Uhr et al 10.1016/j.neuron.2007.11.017 found that rs2235015(T) carriers treated with ABCB1 substrates were more likely to remit. However, this result could not be reproduced in a large (N~900) trial with outpatients with major depression treated with the ABCB1 substrate citalopram (STAR-D study, level 1). According to a recent meta analysis [PMID 25847751], no significant association of antidepressant treatment outcome with this SNP among all studies, but the association remained significant in a subgroup-analysis of all inpatients.
rs2235015 is near the 9 SNPs found within a tight linkage block (r2 >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below. rs2235015 has an r2 value of >0.5 with this group 10.1016/j.neuron.2007.11.017:
[PMID 18382661] Pharmacokinetic genes do not influence response or tolerance to citalopram in the STAR*D sample.
[PMID 18535201] A genome-wide scan for common genetic variants with a large influence on warfarin maintenance dose.
[PMID 21172166] Pharmacogenetics of antidepressant response.
[PMID 22641028] ABCB1 gene variants influence tolerance to selective serotonin reuptake inhibitors in a large sample of Dutch cases with major depressive disorder.
[PMID 22672924] Polymorphisms of the drug transporter gene ABCB1 predict side effects of treatment with cabergoline in patients with PRL adenomas
[PMID 3881999] Tricyclic antidepressants--blood level measurements and clinical outcome: an APA Task Force report. Task Force on the Use of Laboratory Tests in Psychiatry
[PMID 28648553] Escitalopram plasma levels and antidepressant response
[PMID 25188033] Venlafaxine and O-desmethylvenlafaxine concentrations in plasma and cerebrospinal fluid
[PMID 30611837] Duloxetine plasma level and antidepressant response