Kazunari Yoshida1, Malgorzata Maciukiewicz2, Clement C Zai3, Vanessa F Gonçalves4, Eva J Brandl5, Jeffrey A Lieberman6, Herbert Y Meltzer7, Arun K Tiwari4, James L Kennedy8, Daniel J Müller9. 1. Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan. 2. Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Rheumatology, Center of Experimental Rheumatology, University Hospital of Zurich, Zurich, Switzerland. 3. Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. 4. Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. 5. Department of Psychiatry and Psychotherapy, Campus Mitte, Charité Universitätsmedizin Berlin, Berlin, Germany. 6. Department of Psychiatry, College of Physicians and Surgeons, Columbia University, The New York State Psychiatric Institute, New York City, NY, USA. 7. Department of Psychiatry and Behavioral Sciences, Northwestern Feinberg School of Medicine, Evanston, IL, USA. 8. Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada. 9. Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada. Electronic address: daniel.mueller@camh.ca.
Abstract
BACKGROUND: Antipsychotics, especially most of the second-generation antipsychotics, have a high risk for metabolic syndrome and antipsychotic-induced weight gain (AIWG). A promoter variant of the leptin (LEP) gene, -2548G/A (rs7799039), has been associated with AIWG in several studies. The aim of this study was to evaluate this association in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) sample, followed by meta-analysis. METHODS: We investigated the association between rs7799039 and AIWG in a sub-sample of European (N = 164) individuals from the CATIE study. Body mass index (BMI) change and weight gain (presence or absence) was analyzed using ANCOVA and logistic regression, respectively. For the meta-analysis, a literature search was conducted using MEDLINE, Embase, and PsycINFO up to October 2019. The pooled odds ratio was calculated for presence or absence of weight gain (≥7% weight change) using a random effects model. RESULTS: We did not detect an association between rs7799039 and BMI change or weight gain (presence or absence) in the CATIE sample. As for the meta-analysis, we included 12 studies. No significant associations between the LEP rs7799039 polymorphism and AIWG were observed under the allelic genetic model (allele A vs. allele G) (OR = 1.10 [0.71, 1.70], p = .68). In the subgroup analyses of first-episode schizophrenia patients, a significant association between the A-allele and weight gain was observed, respectively (OR = 2.32 [1.41, 3.82], p = .0009). CONCLUSIONS: The present meta-analysis showed no significant effect of rs7799039 on AIWG. However, this variant may influence AIWG in first-episode schizophrenia patients. Further investigation of a larger and more homogenous sample is required to elucidate the role of the LEP gene in AIWG.
BACKGROUND: Antipsychotics, especially most of the second-generation antipsychotics, have a high risk for metabolic syndrome and antipsychotic-induced weight gain (AIWG). A promoter variant of the leptin (LEP) gene, -2548G/A (rs7799039), has been associated with AIWG in several studies. The aim of this study was to evaluate this association in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) sample, followed by meta-analysis. METHODS: We investigated the association between rs7799039 and AIWG in a sub-sample of European (N = 164) individuals from the CATIE study. Body mass index (BMI) change and weight gain (presence or absence) was analyzed using ANCOVA and logistic regression, respectively. For the meta-analysis, a literature search was conducted using MEDLINE, Embase, and PsycINFO up to October 2019. The pooled odds ratio was calculated for presence or absence of weight gain (≥7% weight change) using a random effects model. RESULTS: We did not detect an association between rs7799039 and BMI change or weight gain (presence or absence) in the CATIE sample. As for the meta-analysis, we included 12 studies. No significant associations between the LEP rs7799039 polymorphism and AIWG were observed under the allelic genetic model (allele A vs. allele G) (OR = 1.10 [0.71, 1.70], p = .68). In the subgroup analyses of first-episode schizophreniapatients, a significant association between the A-allele and weight gain was observed, respectively (OR = 2.32 [1.41, 3.82], p = .0009). CONCLUSIONS: The present meta-analysis showed no significant effect of rs7799039 on AIWG. However, this variant may influence AIWG in first-episode schizophreniapatients. Further investigation of a larger and more homogenous sample is required to elucidate the role of the LEP gene in AIWG.
Authors: Claudia Terezia Socol; Alexandra Chira; Maria Antonia Martinez-Sanchez; Maria Angeles Nuñez-Sanchez; Cristina Maria Maerescu; Daniel Mierlita; Alexandru Vasile Rusu; Antonio Jose Ruiz-Alcaraz; Monica Trif; Bruno Ramos-Molina Journal: Int J Mol Sci Date: 2022-04-24 Impact factor: 6.208
Authors: Anastasiia S Boiko; Ivan V Pozhidaev; Diana Z Paderina; Irina A Mednova; Anastasya A Goncharova; Olga Yu Fedorenko; Elena G Kornetova; Arkadiy V Semke; Nikolay A Bokhan; Anton J M Loonen; Svetlana A Ivanova Journal: Genes (Basel) Date: 2022-05-08 Impact factor: 4.141