||possibly less likely to remit on certain antidepressants
||possibly, normal rate of remission on certain antidepressants
||possibly more likely to remit on certain antidepressants
|?|| (A;A) (A;G) (G;G) ||28|
rs10248420 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.
rs10248420 is one of 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.
When treated for depression with citalopram, paroxetine, amitriptyline, or venlafaxine (substrates of the protein encoded by ABCB1), a highly statistically significant association between the overall genetic variability of these SNPs and remission was reported by Uhr et al in a study of ~400 German inpatients.10.1016/j.neuron.2007.11.017. However, this result has to be treated with caution. A well-run, double-blind study of ABCB1 substrate citalopram in depression (STAR-D study) and a following meta-analysis [PMID 25847751] failed to replicate several Uhr et al. results for other ABCB1 SNPs.
The 9 SNPs in the linkage block identified are 10.1016/j.neuron.2007.11.017:
[PMID 19107781] rs10248420 and rs2032583 associated with colonic disease
[PMID 15197162] Identifying candidate causal variants responsible for altered activity of the ABCB1 multidrug resistance gene.
[PMID 22722500] Association study of 27 annotated genes for clozapine pharmacogenetics: validation of preexisting studies and identification of a new candidate gene, ABCB1, for treatment response.