Association of PCK1 with Body Mass Index and Other Metabolic Features in Patients With Psychotropic Treatments.
Weight gain is a major health problem among psychiatric populations. It implicates several receptors and hormones involved in energy balance and metabolism. Phosphoenolpyruvate carboxykinase 1 is a rate-controlling enzyme involved in gluconeogenesis, glyceroneogenesis and cataplerosis and has been related to obesity and diabetes phenotypes in animals and humans. The aim of this study was to investigate the association of phosphoenolpyruvate carboxykinase 1 polymorphisms with metabolic traits in psychiatric patients treated with psychotropic drugs inducing weight gain and in general population samples. One polymorphism (rs11552145G > A) significantly associated with body mass index in the psychiatric discovery sample (n = 478) was replicated in 2 other psychiatric samples (n1 = 168, n2 = 188), with AA-genotype carriers having lower body mass index as compared to G-allele carriers. Stronger associations were found among women younger than 45 years carrying AA-genotype as compared to G-allele carriers (-2.25 kg/m, n = 151, P = 0.009) and in the discovery sample (-2.20 kg/m, n = 423, P = 0.0004). In the discovery sample for which metabolic parameters were available, AA-genotype showed lower waist circumference (-6.86 cm, P = 0.008) and triglycerides levels (-5.58 mg/100 mL, P < 0.002) when compared to G-allele carriers. Finally, waist-to-hip ratio was associated with rs6070157 (proxy of rs11552145, r = 0.99) in a population-based sample (N = 123,865, P = 0.022). Our results suggest an association of rs11552145G > A polymorphism with metabolic-related traits, especially in psychiatric populations and in women younger than 45 years.
From the *Unit of Pharmacogenetics and Clinical Psychopharmacology, Department of Psychiatry, Centre for Psychiatric Neuroscience, †Department of Psychiatry, Centre of Psychiatric Epidemiology and Psychopathology, ‡Department of Psychiatry, Centre for Psychiatric Neuroscience, Lausanne University Hospital, Prilly, Switzerland; §Laboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne; ∥Department of Mental Health and Psychiatry, University Hospital of Geneva, Geneva; ¶Service of Old Age Psychiatry, Department of Psychiatry, Lausanne University Hospital, Prilly; #Department of Medicine, Lausanne University Hospital; **Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital; ††Swiss Institute of Bioinformatics, Lausanne; ‡‡Service of General Psychiatry, Department of Psychiatry, Lausanne University Hospital, Prilly; and §§School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
Núria
N
Saigi-Morgui
Frederik
F
Vandenberghe
Aurélie
A
Delacrétaz
Lina
L
Quteineh
Eva
E
Choong
Mehdi
M
Gholamrezaee
Pierre
P
Magistretti
Jean-Michel
JM
Aubry
Armin
A
von Gunten
Martin
M
Preisig
Enrique
E
Castelao
Peter
P
Vollenweider
Gerard
G
Waeber
Zoltán
Z
Kutalik
Philippe
P
Conus
Chin B
CB
Eap
D000328:Adult; D000367:Age Factors; D015992:Body Mass Index; D005260:Female; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy; D008875:Middle Aged; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011619:Psychotropic Drugs / Q000009:adverse effects* / Q000627:therapeutic use; D012737:Sex Factors; D014280:Triglycerides / Q000097:blood; D055105:Waist Circumference / Q000235:genetics; D065927:Waist-Height Ratio; D015430:Weight Gain / Q000187:drug effects* / Q000235:genetics
D047908:Intracellular Signaling Peptides and Proteins; D011619:Psychotropic Drugs; D014280:Triglycerides; C521898:PCK1 protein, human; D010729:Phosphoenolpyruvate Carboxykinase (GTP)