|(C;C)||1.9||more likely to remit on certain antidepressants.|
|(C;T)||1.9||more likely to remit certain antidepressants.|
|(T;T)||2||less likely to remit on 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. 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 studied reported that ABCB1 SNPs have clinical effect in depression and eight that they do not.
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:
In contrast, [PMID 25487678] reported on two SNPs from the block, rs2032583 and rs2235040, that these SNPs are close to Hardy–Weinberg equilibrium (not inherited together) in their 81% white population. Other results from [PMID 25487678] are unreliable because they picked an antidepressant sertraline, which is, likely, not an ABCB1 substrate [PMID 27918249], as an example of an ABCB1 substrate and treated a majority of patients in the study with it.
[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