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


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.
Department of Public Health & Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
Po-Hsiu
PH
Kuo
Chung-Feng
CF
Kao
Po-Yu
PY
Chen
Chun-Hsin
CH
Chen
Yau-Sheng
YS
Tsai
Mong-Lian
ML
Lu
Ming-Chyi
MC
Huang
D000328:Adult; D001786:Blood Glucose / Q000235:genetics; D015992:Body Mass Index; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D020738:Leptin / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D024821:Metabolic Syndrome / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D011618:Psychotic Disorders / Q000150:complications / Q000235:genetics; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics*; D012559:Schizophrenia / Q000150:complications* / Q000235:genetics; D013624:Taiwan; D055105:Waist Circumference / Q000235:genetics; D055815:Young Adult
D001786:Blood Glucose; C467727:INSIG2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin; C470072:MC4R protein, human; D008565:Membrane Proteins; D044105:Receptor, Melanocortin, Type 4