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Association of variants in SH2B1 and RABEP1 with worsening of low-density lipoprotein and glucose parameters in patients treated with psychotropic drugs.
Delacrétaz, Aurélie; Zdralovic, Adna; Vandenberghe, Frederik; Saigi-Morgui, Nuria; Glatard, Anaïs; Quteineh, Lina; Gholam-Rezaee, Mehdi; Raffoul, Wassim; Applegate, Lee Ann; Jafari, Paris; Gamma, Franziska; von Gunten, Armin; Conus, Philippe; Eap, Chin B.
Afiliação
  • Delacrétaz A; Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
  • Zdralovic A; Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
  • Vandenberghe F; Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
  • Saigi-Morgui N; Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
  • Glatard A; Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
  • Quteineh L; Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
  • Gholam-Rezaee M; Centre of Psychiatric Epidemiology and Psychopathology, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
  • Raffoul W; Department of Plastic, Reconstructive and Hand Surgery, Unit of Regenerative Therapy, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
  • Applegate LA; Department of Plastic, Reconstructive and Hand Surgery, Unit of Regenerative Therapy, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
  • Jafari P; Department of Plastic, Reconstructive and Hand Surgery, Unit of Regenerative Therapy, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
  • Gamma F; Les Toises Psychiatry and Psychotherapy Center, Lausanne, Switzerland.
  • von Gunten A; Service of Old Age Psychiatry, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
  • Conus P; Service of General Psychiatry, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
  • Eap CB; Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland; School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland. Electronic address: chin.e
Gene ; 628: 8-15, 2017 Sep 10.
Article em En | MEDLINE | ID: mdl-28694205
ABSTRACT
Genetic factors associated with Body Mass Index (BMI) have been widely studied over the last decade. We examined whether genetic variants previously associated with BMI in the general population are associated with cardiometabolic parameter worsening in the psychiatric population receiving psychotropic drugs, a high-risk group for metabolic disturbances. Classification And Regression Trees (CARTs) were used as a tool capable of describing hierarchical associations, to pinpoint genetic variants best predicting worsening of cardiometabolic parameters (i.e total, HDL and LDL-cholesterol, triglycerides, body mass index, waist circumference, fasting glucose, and blood pressure) following prescription of psychotropic drugs inducing weight gain in a discovery sample of 357 Caucasian patients. Significant findings were tested for replication in a second Caucasian psychiatric sample (n=140). SH2B1 rs3888190C>A was significantly associated with LDL levels in the discovery and in the replication sample, with A-allele carriers having 0.2mmol/l (p=0.005) and 0.36mmol/l (p=0.007) higher LDL levels compared to others, respectively. G-allele carriers of RABEP1 rs1000940A>G had lower fasting glucose levels compared to others in both samples (-0.16mmol/l; p<0.001 and -0.77mmol/l; p=0.03 respectively). The present study is the first to observe such associations in human subjects, which may in part be explained by a high risk towards dyslipidemia and diabetes in psychiatric patients receiving psychotropic treatments compared to population-based individuals. These results may therefore give new insight into the etiology of LDL-cholesterol and glucose regulation in psychiatric patients under psychotropic drug therapy.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Psicotrópicos / Glicemia / Aumento de Peso / Polimorfismo de Nucleotídeo Único / Proteínas de Transporte Vesicular / Proteínas Adaptadoras de Transdução de Sinal / LDL-Colesterol / Transtornos Mentais Tipo de estudo: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Gene Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Psicotrópicos / Glicemia / Aumento de Peso / Polimorfismo de Nucleotídeo Único / Proteínas de Transporte Vesicular / Proteínas Adaptadoras de Transdução de Sinal / LDL-Colesterol / Transtornos Mentais Tipo de estudo: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Gene Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Suíça