|(C;C)||1.9||7x more likely to respond to certain antidepressants.|
|(C;T)||1.9||7x more likely to respond to certain antidepressants.|
|(T;T)||2||7x less likely to respond to certain antidepressants.|
rs2032583 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 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 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 rs2032583(C) 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 25487678] Finds that the 6-9 SNPs originally reported as usually being co-inherited showed more independence from one another, with rs2235040 and rs9282564 showing the most power to influence time to remission. Remission rate was higher (69-87%) and achieved sooner for carriers of the minor alleles of these SNPs, yet 43% of major allele homozygotes (i.e. rs2235040(G;G) and rs9282564(A;A) individuals) still achieved remission. Study (97 patients total) primarily involved patients prescribed sertraline but also included some prescribed venlafaxine or escitalopram, which like sertraline are thought to be P-gp substrates.
[PMID 15197162] Identifying candidate causal variants responsible for altered activity of the ABCB1 multidrug resistance gene.
[PMID 18424454] ABCB1 (MDR1) genetic variants are associated with methadone doses required for effective treatment of heroin dependence.
[PMID 19844206] Sequence variations of ABCB1, SLC6A2, SLC6A3, SLC6A4, CREB1, CRHR1 and NTRK2: association with major depression and antidepressant response in Mexican-Americans.
[PMID 21172166] Pharmacogenetics of antidepressant response.
[PMID 21827404] The clinical impact of ABCB1 polymorphisms on the treatment of psychiatric diseases.
[PMID 21987299] Associations between variants in the ABCB1 (MDR1) gene and corticosteroid dependence in children with Crohn's disease.
[PMID 22641028] ABCB1 gene variants influence tolerance to selective serotonin reuptake inhibitors in a large sample of Dutch cases with major depressive disorder.
[PMID 22672924] Polymorphisms of the drug transporter gene ABCB1 predict side effects of treatment with cabergoline in patients with PRL adenomas
[PMID 23093106] Detection of frequent ABCB1 polymorphisms by high-resolution melting curve analysis and their effect on breast carcinoma prognosis