rs2235015 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 thus their efficacy or potential for adverse side effects. rs2032583 is near 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.
When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are known to be substrates include citalopram, paroxetine, amitriptyline, and venlafaxine. The relative odds of better response for rs2235015(T) carriers is 7.72 (CI: 2.8-21.3, p=0.000065) based on a study of ~400 primarily Caucasian patients.10.1016/j.neuron.2007.11.017
The 9 SNPs in the linkage block identified are 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.
|qualified_impact||Insufficiently evaluated pharmacogenetic|
[PMID 22672924] Polymorphisms of the drug transporter gene ABCB1 predict side effects of treatment with cabergoline in patients with PRL adenomas