| Geno
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Mag
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Summary
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| (A;A)
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1.1
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possibly higher chances of remission only for inpatients on certain antidepressants
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| (A;G)
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1.1
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possibly higher chances of remission only for inpatients on certain antidepressants
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| (G;G)
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1.1
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possibly lesser chances of remission only for inpatients on certain antidepressants
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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 18382661
] 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.
] Pharmacokinetic genes do not influence response or tolerance to citalopram in the STAR*D sample.
