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

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Version: Final published version
Serval ID
serval:BIB_1BC1C0DFA15B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Influence of CRTC1 Polymorphisms on Body Mass Index and Fat Mass in Psychiatric Patients and the General Adult Population.
Journal
JAMA Psychiatry
Author(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
Contributor(s)
ODEX team
ISSN
2168-622X; 2168-6238 (Electronic)
ISSN-L
2168-622X
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
70
Number
10
Pages
1011-1019
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
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
Yes
Create date
29/10/2013 14:48
Last modification date
31/05/2021 14:30
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