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rs2235040

From SNPedia

Orientationminus
Stabilizedminus
Geno Mag Summary
(A;A) 1.1 possibly higher chances of remission only for inpatients on certain antidepressants
(A;G) 1.1 possibly higher chances of remission only for inpatients on certain antidepressants
(G;G) 1.1 possibly lesser chances of remission only for inpatients on certain antidepressants
ReferenceGRCh38 38.1/142
Chromosome7
Position87536434
GeneABCB1
is asnp
is mentioned by
dbSNPrs2235040
dbSNP (old)rs2235040
ClinGenrs2235040
ebirs2235040
HLIrs2235040
Exacrs2235040
Gnomadrs2235040
Varsomers2235040
LitVarrs2235040
Maprs2235040
PheGenIrs2235040
Biobankrs2235040
1000 genomesrs2235040
hgdprs2235040
ensemblrs2235040
gopubmedrs2235040
geneviewrs2235040
scholarrs2235040
googlers2235040
pharmgkbrs2235040
gwascentralrs2235040
openSNPrs2235040
23andMers2235040
23andMe allrs2235040
SNPshotrs2235040
SNPdbers2235040
MSV3drs2235040
GWAS Ctlgrs2235040
GMAF0.1267
Max Magnitude1.1
? (A;A) (A;G) (G;G) 28

rs2235040 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein 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. However, the link between the increased brain concentrations of antidepressants and a clinically significant response is unconfirmed. In clinic, even the lower concentrations of drugs may achieve sufficient antidepressant effect, and the dose of the drug can be adjusted upwards until the patient responds. According to a recent review [PMID 27918249], ten studies reported that ABCB1 SNPs have clinical effect in depression and eight - that they do not.


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 rs2235040(A) carriers treated with ABCB1 substrates were more likely to remit. However, this result failed to reproduce in a large (900 outpatient subjects) and better designed double-blind study of a well-researched ABCB1 substrate citalopram in depression (STAR-D study). According to a recent meta analysis [PMID 25847751], no significant association of antidepressant treatment outcome with this SNP. There was a significant association with treatment outcome in the inpatients subsample but data regarding rs2235040 and treatment outcome among inpatients entirely stemmed from the study by Uhr et al.

The 9 SNPs in the linkage block identified are 10.1016/j.neuron.2007.11.017:


In contrast, [PMID 25487678] reported on two SNPs from the block, rs2032583 and rs2235040, that these SNPs are in a weak disequilibrium (not always inherited together) in their 81% white population. Other results from [PMID 25487678] are unreliable because the authors used an antidepressant sertraline, which is, likely, not an ABCB1 substrate [PMID 27918249], as an example of an ABCB1 substrate and treated most of the patients in the study with sertraline.



[PMID 18382661OA-icon.png] Pharmacokinetic genes do not influence response or tolerance to citalopram in the STAR*D sample.


[PMID 22641028] ABCB1 gene variants influence tolerance to selective serotonin reuptake inhibitors in a large sample of Dutch cases with major depressive disorder.