Polymorphisms of INSIG2, MC4R, and LEP are associated with obesity-and metabolic-related traits in schizophrenic patients

Po Hsiu Kuo, Chung Feng Kao, Po Yu Chen, Chun Hsin Chen, Yau Sheng Tsai, Mong Lian Lu, Ming Chyi Huang

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)705-711
Number of pages7
JournalJournal of Clinical Psychopharmacology
Volume31
Issue number6
DOIs
Publication statusPublished - Dec 2011

Fingerprint

Receptor, Melanocortin, Type 4
Obesity
Genes
Schizophrenia
Waist Circumference
Insulin
HDL Cholesterol
Insulin Resistance
Fasting
Body Mass Index
Homeostasis
Community Psychiatry
Leptin Receptors
Glucose
Rehabilitation Centers
Community Hospital
Psychiatric Hospitals
Leptin
Metabolic Networks and Pathways
Taiwan

Keywords

  • INSIG2
  • LEP
  • MC4R
  • metabolic syndrome
  • obesity
  • schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Polymorphisms of INSIG2, MC4R, and LEP are associated with obesity-and metabolic-related traits in schizophrenic patients. / Kuo, Po Hsiu; Kao, Chung Feng; Chen, Po Yu; Chen, Chun Hsin; Tsai, Yau Sheng; Lu, Mong Lian; Huang, Ming Chyi.

In: Journal of Clinical Psychopharmacology, Vol. 31, No. 6, 12.2011, p. 705-711.

Research output: Contribution to journalArticle

@article{5fa46a7f99a245e2a2873a1d0a2c037c,
title = "Polymorphisms of INSIG2, MC4R, and LEP are associated with obesity-and metabolic-related traits in schizophrenic patients",
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.",
keywords = "INSIG2, LEP, MC4R, metabolic syndrome, obesity, schizophrenia",
author = "Kuo, {Po Hsiu} and Kao, {Chung Feng} and Chen, {Po Yu} and Chen, {Chun Hsin} and Tsai, {Yau Sheng} and Lu, {Mong Lian} and Huang, {Ming Chyi}",
year = "2011",
month = "12",
doi = "10.1097/JCP.0b013e318234ee84",
language = "English",
volume = "31",
pages = "705--711",
journal = "Journal of Clinical Psychopharmacology",
issn = "0271-0749",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

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 - 2011/12

Y1 - 2011/12

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.

AB - 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.

KW - INSIG2

KW - LEP

KW - MC4R

KW - metabolic syndrome

KW - obesity

KW - schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=80755163168&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80755163168&partnerID=8YFLogxK

U2 - 10.1097/JCP.0b013e318234ee84

DO - 10.1097/JCP.0b013e318234ee84

M3 - Article

C2 - 22020349

AN - SCOPUS:80755163168

VL - 31

SP - 705

EP - 711

JO - Journal of Clinical Psychopharmacology

JF - Journal of Clinical Psychopharmacology

SN - 0271-0749

IS - 6

ER -