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

OBJECTIVE: 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. SUBJECTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: This is the first study to link and associate DRD2 variants with the comorbidity of T2D and MDD.