ABCB1 ( MDR1) polymorphisms and antidepressant response in geriatric depression

Objective Variation in the ATP-binding cassette, subfamily B, member 1 transporter (ABCB1) (multidrug-resistance gene 1) gene has been investigated as a predictor of response to treatment with a variety of medications such as antiarrhythmics, chemotherapeutic agents, anti-HIV medications, and some psychotropics. The ABCB1 gene product, P-glycoprotein, affects the transport of drugs out of many cell types, including endothelial cells at the blood-brain barrier. We sought to determine if ABCB1 polymorphisms predict response to antidepressant treatment in geriatric patients. Methods We compared the effects of ABCB1 genetic variation on the therapeutic response to paroxetine, a P-glycoprotein substrate, and to mirtazapine, which is not thought to be transported by ABCB1, in a sample of 246 elderly patients with major depression treated in a clinical trial setting. A total of 15 single nucleotide polymorphisms in the ABCB1 gene were assessed in each patient. Two of these ABCB1 single nucleotide polymorphisms were earlier reported to predict treatment response in patients prescribed with P-glycoprotein substrate antidepressants. Results The two earlier identified ABCB1 markers for antidepressant response predicted time to remission in our paroxetine-treated patients, but not in the mirtazapine-treated patients. These results replicate the published findings of others. If a Bonferroni correction for type I error is made, our results do not reach the criteria for statistical significance. However, the Bonferroni correction may be too conservative given the strong linkage disequilibrium among some of the markers and our aim to replicate the earlier published findings. Conclusion Our study provides confirmation that certain ABCB1 polymorphisms predict response to substrate medications in geriatric patients. Pharmacogenetics and Genomics 20: 467-475 (C) c 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.