Genetic Variation in the GCG and in the GLP1R Genes and Antipsychotic-Induced Weight Gain

Abstract

Aim: GLP-1 plays a key role in glucose metabolism and influences antipsychotic-induced weight gain (AIWG). Our study is the first to investigate the encoding gene, GCG, and the GLP-1 receptor gene, GLP1R, and association with AIWG. Materials & methods: In 216 schizophrenic patients treated with antipsychotics for up to 14 weeks, we investigated four GCG and 33 GLP1R polymorphisms. Statistical analyses were conducted using SPSS, Haploview 4.2, UNPHASED 3.1.4 and the R-package mbmdr. Results: We observed association of rs13429709 near GCG with AIWG (p_corr = 0.044) in patients of European ancestry receiving olanzapine or clozapine (n = 87). We also found significant gene–gene interaction between rs13429709 and rs2268639 in GLP1R. Only nonsignificant trends were observed for GLP1R polymorphisms with AIWG. Conclusion: We found significant association of rs13429709 with AIWG. Although there was no significant finding for GLP1R, the observed trends and interaction suggest this to be an interesting gene for further examination.

Original submitted 17 October 2013; Revision submitted 11 December 2013

KEYWORDS::

• antipsychotic-induced weight gain
• clozapine
• GCG
• GLP1R
• olanzapine
• pharmacogenetics

Financial & competing interests disclosure

HY Meltzer has received grants or is or was a consultant to Abbott Labs, ACADIA, Alkemes, Bristol Myers Squibb, DaiNippon Sumitomo, Eli Lilly, EnVivo, Janssen, Otsuka, Pfizer, Roche, Sunovion and BiolineRx. He is also a shareholder of ACADIA and GlaxoSmithKline. In the past 3 years JA Lieberman reports having received research funding or is a member of the advisory board of Allon, Alkermes Bioline, GlaxoSmithKline Intracellular Therapies, Lilly, Merck, Novartis, Pfizer, Pierre Fabre, Psychogenics, F Hoffmann-La Roche Ltd, Sepracor (Sunovion) and Targacept. He has also received no direct financial compensation or salary support for participation in this research, or for consulting or advisory board activities. JL Kennedy has been a consultant to GlaxoSmithKline, Sanofi-Aventis and Dainippon-Sumitomo. AK Tiwari is the recipient of NARSAD 2010 Young Investigator Award. NI Chowdhury received OMHF Research Studentship. CC Zai is the recipient of NARSAD Young Investigator Award; postdoctoral fellowship from the American Foundation for Suicide Prevention (2PDF-00065-1208-0609-1209); and Eli Lilly Canada. DJ Müller received CIHR operating grant (Genetics of antipsychotics-induced metabolic syndrome, MOP 89853); NARSAD Independent Investigator Award, Early Researcher Award by the Ministry of Research and Innovation of Ontario, CIHR Michael Smith New Investigator Salary Prize for Research in Schizophrenia and OMHF New Investigator Fellowship. JL Kennedy is the recipient of a CIHR operating grant. The funding sources did not have any influence on study design, data analysis and writing of the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

HY Meltzer has received grants or is or was a consultant to Abbott Labs, ACADIA, Alkemes, Bristol Myers Squibb, DaiNippon Sumitomo, Eli Lilly, EnVivo, Janssen, Otsuka, Pfizer, Roche, Sunovion and BiolineRx. He is also a shareholder of ACADIA and GlaxoSmithKline. In the past 3 years JA Lieberman reports having received research funding or is a member of the advisory board of Allon, Alkermes Bioline, GlaxoSmithKline Intracellular Therapies, Lilly, Merck, Novartis, Pfizer, Pierre Fabre, Psychogenics, F Hoffmann-La Roche Ltd, Sepracor (Sunovion) and Targacept. He has also received no direct financial compensation or salary support for participation in this research, or for consulting or advisory board activities. JL Kennedy has been a consultant to GlaxoSmithKline, Sanofi-Aventis and Dainippon-Sumitomo. AK Tiwari is the recipient of NARSAD 2010 Young Investigator Award. NI Chowdhury received OMHF Research Studentship. CC Zai is the recipient of NARSAD Young Investigator Award; postdoctoral fellowship from the American Foundation for Suicide Prevention (2PDF-00065-1208-0609-1209); and Eli Lilly Canada. DJ Müller received CIHR operating grant (Genetics of antipsychotics-induced metabolic syndrome, MOP 89853); NARSAD Independent Investigator Award, Early Researcher Award by the Ministry of Research and Innovation of Ontario, CIHR Michael Smith New Investigator Salary Prize for Research in Schizophrenia and OMHF New Investigator Fellowship. JL Kennedy is the recipient of a CIHR operating grant. The funding sources did not have any influence on study design, data analysis and writing of the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.