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rs10248420

From SNPedia

Orientationplus
Stabilizedplus
Geno Mag Summary
(A;A) 1.1 possibly less likely to remit on certain antidepressants
(A;G) 0 possibly, normal rate of remission on certain antidepressants
(G;G) 1.1 possibly more likely to remit on certain antidepressants
ReferenceGRCh38 38.1/141
Chromosome7
Position87535670
GeneABCB1
is asnp
is mentioned by
dbSNPrs10248420
dbSNP (old)rs10248420
ClinGenrs10248420
ebirs10248420
HLIrs10248420
Exacrs10248420
Gnomadrs10248420
Varsomers10248420
LitVarrs10248420
Maprs10248420
PheGenIrs10248420
Biobankrs10248420
1000 genomesrs10248420
hgdprs10248420
ensemblrs10248420
gopubmedrs10248420
geneviewrs10248420
scholarrs10248420
googlers10248420
pharmgkbrs10248420
gwascentralrs10248420
openSNPrs10248420
23andMers10248420
23andMe allrs10248420
SNPshotrs10248420
SNPdbers10248420
MSV3drs10248420
GWAS Ctlgrs10248420
GMAF0.3476
Max Magnitude1.1
? (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 15197162OA-icon.png] 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.