title: Relaxin polymorphisms associated with metabolic disturbance in patients treated with antipsychotics.
abstract: People with schizophrenia have an increased risk of metabolic syndrome, with consequent elevated morbidity and mortality, largely due to cardiovascular disease. Metabolic disorders comprise obesity, dyslipidemia and elevated levels of triglycerides, hypertension, and disturbed insulin and glucose metabolism. The elevated risk of metabolic syndrome in individuals suffering from schizophrenia is believed to be multifactorial, related to a genetic predisposition, lifestyle characteristics and treatment with antipsychotic medications. Relaxin 3 (RLN3, also known as INSL7) is a recently identified member of the insulin/relaxin superfamily that plays a role in the regulation of appetite and body weight control. RLN3 stimulates relaxin-3 receptor 1 (relaxin/insulin-like family peptide receptor 3, RXFP3) and relaxin receptor 2 (relaxin/insulin-like family peptide receptor 4, RXFP4). We have investigated the role of ten polymorphisms in these genes (RLN3 rs12327666, rs1982632, and rs7249702, RLN3R1 rs42868, rs6861957, rs7702361, and rs35399, and RLN3R2 rs11264422, rs1018730 and rs12124383) in the occurrence of metabolic syndrome phenotypes (obesity, diabetes, hypercholesterolemia, hypertrigyceridemia, and hypertension) in a cross-sectional cohort of 419 US Caucasian patients treated with antipsychotic drugs. We found several associations between relaxin polymorphisms and hypecholesterolemia, obesity and diabetes, suggesting a role for the relaxin/insulin pathway in the development of metabolic disturbance observed in patients treated with antipsychotics.
authors.affiliation: Optimal Medicine Ltd., Warwick Enterprise Park, Wellesbourne, Warwick, UK.
authors.forename: Janet
authors.initials: J
authors.lastname: Munro
authors.forename: Olivia
authors.initials: O
authors.lastname: Skrobot
authors.forename: May
authors.initials: M
authors.lastname: Sanyoura
authors.forename: Victoria
authors.initials: V
authors.lastname: Kay
authors.forename: Margaret T
authors.initials: MT
authors.lastname: Susce
authors.forename: Paul E A
authors.initials: PE
authors.lastname: Glaser
authors.forename: Jose
authors.initials: J
authors.lastname: de Leon
authors.forename: Alexandra I F
authors.initials: AI
authors.lastname: Blakemore
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Arranz
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015992:Body Mass Index; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000150:complications / Q000235:genetics / Q000378:metabolism; D007629:Kentucky; D008297:Male; D008659:Metabolic Diseases / Q000139:chemically induced / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D018000:Receptors, Peptide / Q000235:genetics* / Q000378:metabolism; D012065:Relaxin / Q000235:genetics* / Q000378:metabolism; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D044465:White People
chemical_list: D014150:Antipsychotic Agents; C480238:RLN3 protein, human; C410092:RXFP3 protein, human; C480239:RXFP4 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D012065:Relaxin