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Polymorphisms of INSIG2, MC4R, and LEP are associated with obesity- and metabolic-related traits in schizophrenic patients.
J Clin Psychopharmacol 2011; 31(6):705-11JC

Abstract

BACKGROUND

Schizophrenic patients have a high prevalence of metabolic adversities. Previous studies have suggested some candidate genes for obesity- and metabolic-related traits, including the insulin-induced gene (INSIG2), melanocortin 4 receptor gene (MC4R), and leptin and leptin receptor genes (LEP and LEPR). We aimed to investigate the associations between these genes and metabolic disturbances in patients with schizophrenia in Taiwan.

METHODS

Patients with a diagnosis of schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were recruited from 36 community psychiatric rehabilitation centers or hospitals in Taipei. A total of 650 subjects were enrolled, and 577 were included in the genetic analyses. The anthropometric (body mass index, waist circumference [WC], and blood pressure) and biochemical measurements (fasting plasma glucose, insulin, triglyceride, high-density lipoprotein cholesterol, and Homeostasis Model of Assessment - Insulin Resistance index [HOMA-IR]) were assessed. Seven loci in the 4 genes were genotyped using standard TaqMan assays. Genetic association analyses were conducted for binary and quantitative measurements of the previously mentioned traits. Obese patients with schizophrenia exhibited more metabolic disturbances than nonobese patients.

RESULTS AND CONCLUSIONS

Our data showed that INSIG2 was significantly associated with fasting plasma glucose (for rs17587100, P < 0.0001), MC4R was associated with WC (for rs2229616, P = 0.005), and LEP was associated with body mass index and WC (for rs7799039, P < 0.01). In addition, these loci showed suggestive associations with traits including high-density lipoprotein cholesterol and triglyceride, metabolic syndrome, insulin level, and HOMA-IR index (P = 0.05). In addition to the effect from antipsychotic medications and an unhealthy lifestyle, genetic factors also contribute to the high prevalence of obesity and metabolic disturbances in patients with schizophrenia, especially genes involved in metabolic-related pathways.

Authors+Show Affiliations

Department of Public Health & Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22020349

Citation

Kuo, Po-Hsiu, et al. "Polymorphisms of INSIG2, MC4R, and LEP Are Associated With Obesity- and Metabolic-related Traits in Schizophrenic Patients." Journal of Clinical Psychopharmacology, vol. 31, no. 6, 2011, pp. 705-11.
Kuo PH, Kao CF, Chen PY, et al. Polymorphisms of INSIG2, MC4R, and LEP are associated with obesity- and metabolic-related traits in schizophrenic patients. J Clin Psychopharmacol. 2011;31(6):705-11.
Kuo, P. H., Kao, C. F., Chen, P. Y., Chen, C. H., Tsai, Y. S., Lu, M. L., & Huang, M. C. (2011). Polymorphisms of INSIG2, MC4R, and LEP are associated with obesity- and metabolic-related traits in schizophrenic patients. Journal of Clinical Psychopharmacology, 31(6), pp. 705-11. doi:10.1097/JCP.0b013e318234ee84.
Kuo PH, et al. Polymorphisms of INSIG2, MC4R, and LEP Are Associated With Obesity- and Metabolic-related Traits in Schizophrenic Patients. J Clin Psychopharmacol. 2011;31(6):705-11. PubMed PMID: 22020349.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Polymorphisms of INSIG2, MC4R, and LEP are associated with obesity- and metabolic-related traits in schizophrenic patients. AU - Kuo,Po-Hsiu, AU - Kao,Chung-Feng, AU - Chen,Po-Yu, AU - Chen,Chun-Hsin, AU - Tsai,Yau-Sheng, AU - Lu,Mong-Lian, AU - Huang,Ming-Chyi, PY - 2011/10/25/entrez PY - 2011/10/25/pubmed PY - 2012/2/23/medline SP - 705 EP - 11 JF - Journal of clinical psychopharmacology JO - J Clin Psychopharmacol VL - 31 IS - 6 N2 - BACKGROUND: Schizophrenic patients have a high prevalence of metabolic adversities. Previous studies have suggested some candidate genes for obesity- and metabolic-related traits, including the insulin-induced gene (INSIG2), melanocortin 4 receptor gene (MC4R), and leptin and leptin receptor genes (LEP and LEPR). We aimed to investigate the associations between these genes and metabolic disturbances in patients with schizophrenia in Taiwan. METHODS: Patients with a diagnosis of schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were recruited from 36 community psychiatric rehabilitation centers or hospitals in Taipei. A total of 650 subjects were enrolled, and 577 were included in the genetic analyses. The anthropometric (body mass index, waist circumference [WC], and blood pressure) and biochemical measurements (fasting plasma glucose, insulin, triglyceride, high-density lipoprotein cholesterol, and Homeostasis Model of Assessment - Insulin Resistance index [HOMA-IR]) were assessed. Seven loci in the 4 genes were genotyped using standard TaqMan assays. Genetic association analyses were conducted for binary and quantitative measurements of the previously mentioned traits. Obese patients with schizophrenia exhibited more metabolic disturbances than nonobese patients. RESULTS AND CONCLUSIONS: Our data showed that INSIG2 was significantly associated with fasting plasma glucose (for rs17587100, P < 0.0001), MC4R was associated with WC (for rs2229616, P = 0.005), and LEP was associated with body mass index and WC (for rs7799039, P < 0.01). In addition, these loci showed suggestive associations with traits including high-density lipoprotein cholesterol and triglyceride, metabolic syndrome, insulin level, and HOMA-IR index (P = 0.05). In addition to the effect from antipsychotic medications and an unhealthy lifestyle, genetic factors also contribute to the high prevalence of obesity and metabolic disturbances in patients with schizophrenia, especially genes involved in metabolic-related pathways. SN - 1533-712X UR - https://www.unboundmedicine.com/medline/citation/22020349/Polymorphisms_of_INSIG2_MC4R_and_LEP_are_associated_with_obesity__and_metabolic_related_traits_in_schizophrenic_patients_ L2 - http://Insights.ovid.com/pubmed?pmid=22020349 DB - PRIME DP - Unbound Medicine ER -