Genetic Variations within Metalloproteinases Impact on the Prophylaxis of Depressive Phases in Bipolar Patients

Abstract

Background: The genetic background of the antidepressant response to pharmacological treatment in bipolar disorder (BD) remains elusive. This issue is of primary relevance in that the depressive phases of BD are difficult to treat and they are associated with suicide. Aim: We investigated the role of a set of genetic variations (single-nucleotide polymorphisms) harbored by matrix metalloproteinases (MMPs) as predictors of response to treatment in depressed BD patients. Methods: 654 BD patients from the publicly available Systematic Treatment Enhancement Program for Bipolar Disorder study were investigated. The outcome was the number of depressive events corrected by the number of times patients were assessed. Clinical and sociodemographic variables were tested as possible stratification factors and included in the analysis if necessary. Genetic predictors were 43 SNPs harbored by 17 MMPs. Imputation, quality check and pruning were conducted according to standards. Results were corrected for multitesting. Results: rs486055 (MMP-10) was associated with the outcome. TT homozygotes had 5.08 ± 3.51 events, CT had 3.47 ± 3.18 and CC had 2.57 ± 2.96 depressive events corrected for the times they had been assessed. The time during which BD patients were observed was not significantly different between the rs486055 genotypes. We found evidence that MMP-10 may be a mediator of the number of depressive phases during BD. Due to the limits of the study including the small-to-medium sample size, the naturalistic design and the possible occurrence of false-positive findings, independent analyses are warranted.