Influence of CRTC1 Polymorphisms on Body Mass Index and Fat Mass in Psychiatric Patients and the General Adult Population.

Détails

Ressource 1Télécharger: BIB_1BC1C0DFA15B.P001.pdf (163.44 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_1BC1C0DFA15B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Influence of CRTC1 Polymorphisms on Body Mass Index and Fat Mass in Psychiatric Patients and the General Adult Population.
Périodique
JAMA Psychiatry
Auteur(s)
Choong E., Quteineh L., Cardinaux J.R., Gholam-Rezaee M., Vandenberghe F., Dobrinas M., Bondolfi G., Etter M., Holzer L., Magistretti P., von Gunten A., Preisig M., Vollenweider P., Beckmann J.S., Pralong F.P., Waeber G., Kutalik Z., Conus P., Bochud M., Eap C.B., ODEX team
Contributeur(s)
ODEX team
ISSN
2168-622X; 2168-6238 (Electronic)
ISSN-L
2168-622X
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
70
Numéro
10
Pages
1011-1019
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish
Résumé
IMPORTANCE There is a high prevalence of obesity in psychiatric patients, possibly leading to metabolic complications and reducing life expectancy. The CREB-regulated transcription coactivator 1 (CRTC1) gene is involved in energy balance and obesity in animal models, but its role in human obesity is unknown. OBJECTIVE To determine whether polymorphisms within the CRTC1 gene are associated with adiposity markers in psychiatric patients and the general population. DESIGN, SETTING, AND PARTICIPANTS Retrospective and prospective data analysis and population-based samples at Lausanne and Geneva university hospitals in Switzerland and a private clinic in Lausanne, Switzerland. The effect of 3 CRTC1 polymorphisms on body mass index (BMI) and/or fat mass was investigated in a discovery cohort of psychiatric outpatients taking weight gain-inducing psychotropic drugs (sample 1, n = 152). The CRTC1 variant that was significantly associated with BMI and survived Bonferroni corrections for multiple comparison was then replicated in 2 independent psychiatric samples (sample 2, n = 174 and sample 3, n = 118) and 2 white population-based samples (sample 4, n = 5338 and sample 5, n = 123 865). INTERVENTION Noninterventional studies. MAIN OUTCOME AND MEASURE Difference in BMI and/or fat mass between CRTC1 genotype groups. RESULTS Among the CRTC1 variants tested in the first psychiatric sample, only rs3746266A>G was associated with BMI (Padjusted = .003). In the 3 psychiatric samples, carriers of the rs3746266 G allele had a lower BMI than noncarriers (AA genotype) (sample 1, P = .001; sample 2, P = .05; and sample 3, P = .0003). In the combined analysis, excluding patients taking other weight gain-inducing drugs, G allele carriers (n = 98) had a 1.81-kg/m2 lower BMI than noncarriers (n = 226; P < .0001). The strongest association was observed in women younger than 45 years, with a 3.87-kg/m2 lower BMI in G allele carriers (n = 25) compared with noncarriers (n = 48; P < .0001), explaining 9% of BMI variance. In the population-based samples, the T allele of rs6510997C>T (a proxy of the rs3746266 G allele; r2 = 0.7) was associated with lower BMI (sample 5, n = 123 865; P = .01) and fat mass (sample 4, n = 5338; P = .03). The strongest association with fat mass was observed in premenopausal women (n = 1192; P = .02). CONCLUSIONS AND RELEVANCE These findings suggest that CRTC1 contributes to the genetics of human obesity in psychiatric patients and the general population. Identification of high-risk subjects could contribute to a better individualization of the pharmacological treatment in psychiatry.
Pubmed
Web of science
Open Access
Oui
Création de la notice
29/10/2013 15:48
Dernière modification de la notice
20/08/2019 13:52
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