Multilocus Genetic Profile Reflecting Low Dopaminergic Signaling Is Directly Associated with Obesity and Cardiometabolic Disorders Due to Antipsychotic Treatment

Treatment with second-generation antipsychotics (SGAs) can cause obesity and other cardiometabolic disorders linked to D2 receptor (DRD2) genotypes affecting dopaminergic (DA) activity, within reward circuits. We explored the relationship of alterations single genetic polymorphisms DRD2 rs1799732 (NG_008841.1:g.4750dup -> C), rs6277 (NG_008841.1:g.67543C>T), COMT rs4680 (NG_011526.1:g.27009G>A), VNTR in both DRD4 NC_000011.10 (637269-640706) DAT1 NC_000005.10 (1392794-1445440), as well a multilocus profile score (MLGP). A total 285 psychiatric patients treated SGAs for at least three months were selected. Cardiometabolic parameters classified according ATP-III WHO criteria. Blood samples taken routinely biochemical assays PCR genotyping. Obesity (BMI, waist (W)), high diastolic blood pressure (DBP), hypertriglyceridemia (HTG) present those variants related low activity: InsIns genotype (BMI: OR: 2.91 [1.42–5.94]), DRD4-VNTR-L allele (W: 1.73 [1.04–2.87]) 9R9R variant DAT1-VNTR 2.73 [1.16–6.40]; DBP: 3.33 [1.54–7.31]; HTG: 4.38 [1.85–10.36]). MLGP indicated higher risk suffering 1.23 [1.05–1.45]; W: 1.18 [1.03–1.34]; 1.22 [1.06–1.41]; 1.20 [1.04–1.39]). The was more sensitive detecting these alterations. Low system function would contribute increased obesity, BDP, HTG following long-term SGA treatment.