Linkage and association of novel DRD2 variants to the comorbidity of type 2 diabetes and depression.

Abstract

The dopamine receptor 2 (DRD2) binds dopamine in both central tissues (e.g., basal ganglia, pituitary gland) and peripheral tissues (e.g., adrenal gland, kidneys, intestine) and mediates dopamine actions in cognition, emotional processing, and prolactin-secretion inhibition and stimulation, and in DRD2-/- knockout mice insulin secretion is impaired. Variants in or around the DRD2 gene have been implicated in major depressive disorder (MDD), schizophrenia, obesity, and type 2 diabetes (T2D) but not in comorbid MDD-T2D patients; DRD2 agonists (e.g., bromocriptine) are approved treatments in T2D. This study aimed to detect whether the DRD2 gene plays a role in T2D, MDD, and T2D-MDD comorbidity in Italian families. In 212 Italian families with T2D and MDD, we investigated the presence of linkage and linkage disequilibrium of variants in the DRD2 gene with T2D and/or MDD. A test was considered statistically significant if p was <0.05. We found 3 novel variants (rs6276, rs35608204, and rs1800499) significantly linked to and/or associated with the risk of T2D and 1 novel variant (rs112646785) significantly linked and associated to the comorbidity of T2D and MDD. This is the first study to link and associate DRD2 variants with the comorbidity of T2D and MDD.