Association of variants in SH2B1 and RABEP1 with worsening of low-density lipoprotein and glucose parameters in patients treated with psychotropic drugs.

Détails

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Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_0B119BA2C151
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Association of variants in SH2B1 and RABEP1 with worsening of low-density lipoprotein and glucose parameters in patients treated with psychotropic drugs.
Périodique
Gene
Auteur(s)
Delacrétaz A., Zdralovic A., Vandenberghe F., Saigi-Morgui N., Glatard A., Quteineh L., Gholam-Rezaee M., Raffoul W., Applegate L.A., Jafari P., Gamma F., von Gunten A., Conus P., Eap C.B.
ISSN
1879-0038 (Electronic)
ISSN-L
0378-1119
Statut éditorial
Publié
Date de publication
10/09/2017
Peer-reviewed
Oui
Volume
628
Pages
8-15
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
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.

Mots-clé
Adaptor Proteins, Signal Transducing/genetics, Blood Glucose/drug effects, Body Mass Index, Cholesterol, LDL/blood, Cohort Studies, Genotype, Humans, Mental Disorders/complications, Mental Disorders/drug therapy, Phenotype, Polymorphism, Single Nucleotide, Prospective Studies, Psychotropic Drugs/adverse effects, Vesicular Transport Proteins/genetics, Weight Gain/drug effects, Weight Gain/genetics, Dyslipidemia, Metabolic syndrome in psychiatry, Pharmacogenetics of psychotropic drugs, RABEP1, SH2B1, Type 2 diabetes
Pubmed
Web of science
Création de la notice
03/08/2017 14:46
Dernière modification de la notice
20/08/2019 13:32
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