Multilocus Genetic Profile Reflecting Low Dopaminergic Signaling Is Directly Associated with Obesity and Cardiometabolic Disorders Due to Antipsychotic Treatment
Aurora Arrue,
Olga Olivas,
Leire Erkoreka,
Francisco Jose Alvarez,
Ainara Arnaiz,
Noemi Varela,
Ainhoa Bilbao,
Jose-Julio Rodríguez,
María Teresa Moreno-Calle,
Estibaliz Gordo,
Elena Marín,
Javier Garcia-Cano,
Estela Saez,
Miguel Ángel Gonzalez-Torres,
Mercedes Zumárraga,
Nieves Basterreche
Affiliations
Aurora Arrue
Mental Health Network Group, BioCruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain
Olga Olivas
Mental Health Network Group, BioCruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain
Leire Erkoreka
Mental Health Network Group, BioCruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain
Francisco Jose Alvarez
Research Unit, Cruces University Hospital, Osakidetza Basque Health Service, 48903 Barakaldo, Spain
Ainara Arnaiz
Mental Health Network Group, BioCruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain
Noemi Varela
Mental Health Network Group, BioCruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain
Ainhoa Bilbao
Animal Research Facility, BioCruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain
Jose-Julio Rodríguez
Department of Neurosciences, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU, 48940 Leioa, Spain
María Teresa Moreno-Calle
Mental Health Network Group, BioCruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain
Estibaliz Gordo
Bizkaia Mental Health Network, Zamudio Hospital, Osakidetza Basque Health Service, 48170 Zamudio, Spain
Elena Marín
Mental Health Network Group, BioCruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain
Javier Garcia-Cano
Alternatives to Hospitalization in Bilbao, Bizkaia Mental Health Network, Osakidetza Basque Health Service, 48903 Bilbao, Spain
Estela Saez
Mental Health Network Group, BioCruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain
Miguel Ángel Gonzalez-Torres
Department of Neurosciences, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU, 48940 Leioa, Spain
Mercedes Zumárraga
Mental Health Network Group, BioCruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain
Nieves Basterreche
Functional Neuroanatomy, BioCruces Bizkaia Health Research Institute, Ikerbasque Basque Foundation for Science, 48903 Barakaldo, Spain
Treatment with second-generation antipsychotics (SGAs) can cause obesity and other cardiometabolic disorders linked to D2 receptor (DRD2) and to genotypes affecting dopaminergic (DA) activity, within reward circuits. We explored the relationship of cardiometabolic alterations with single genetic polymorphisms DRD2 rs1799732 (NG_008841.1:g.4750dup -> C), DRD2 rs6277 (NG_008841.1:g.67543C>T), COMT rs4680 (NG_011526.1:g.27009G>A), and VNTR in both DRD4 NC_000011.10 (637269-640706) and DAT1 NC_000005.10 (1392794-1445440), as well as with a multilocus genetic profile score (MLGP). A total of 285 psychiatric patients treated with SGAs for at least three months were selected. Cardiometabolic parameters were classified according to ATP-III and WHO criteria. Blood samples were taken for routinely biochemical assays and PCR genotyping. Obesity (BMI, waist (W)), high diastolic blood pressure (DBP), and hypertriglyceridemia (HTG) were present in those genetic variants related to low dopaminergic activity: InsIns genotype in rs1799732 (BMI: OR: 2.91 [1.42–5.94]), DRD4-VNTR-L allele (W: OR: 1.73 [1.04–2.87]) and 9R9R variant in DAT1-VNTR (W: OR: 2.73 [1.16–6.40]; high DBP: OR: 3.33 [1.54–7.31]; HTG: OR: 4.38 [1.85–10.36]). A low MLGP score indicated a higher risk of suffering cardiometabolic disorders (BMI: OR: 1.23 [1.05–1.45]; W: OR: 1.18 [1.03–1.34]; high DBP: OR: 1.22 [1.06–1.41]; HTG: OR: 1.20 [1.04–1.39]). The MLGP score was more sensitive for detecting the risk of suffering these alterations. Low dopaminergic system function would contribute to increased obesity, BDP, and HTG following long-term SGA treatment.
