Hostname: page-component-78c5997874-g7gxr Total loading time: 0 Render date: 2024-11-15T09:19:41.327Z Has data issue: false hasContentIssue false
  • English
  • Français

Apolipoprotein-E gene variants associated with cardiovascular risk factors in antipsychotic recipients

Published online by Cambridge University Press:  16 April 2020

D. Clark ,
O.A. Skrobot ,
I. Adebiyi ,
M.T. Susce ,
J. de Leon ,
AI.F. Blakemore  and
M.J. Arranz
D. Clark
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, King's College, 1, Windsor Walk, PO51, LondonSE5 8AF, UK
O.A. Skrobot
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, King's College, 1, Windsor Walk, PO51, LondonSE5 8AF, UK
I. Adebiyi
Affiliation:
Section of Genomic Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, East Acton, LondonW12 0NN, UK
M.T. Susce
Affiliation:
University of Kentucky, Mental Health Research Center at Eastern State Hospital, Lexington, KY, USA
J. de Leon
Affiliation:
University of Kentucky, Mental Health Research Center at Eastern State Hospital, Lexington, KY, USA
AI.F. Blakemore
Affiliation:
Section of Genomic Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, East Acton, LondonW12 0NN, UK
M.J. Arranz*
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, King's College, 1, Windsor Walk, PO51, LondonSE5 8AF, UK
*
*Corresponding author. E-mail address:[email protected] (M.J. Arranz).
Get access

Abstract

Interest exists in identifying the factors that specifically contribute to the increased prevalence of cardiovascular disease observed in psychiatric disease. The apolipoprotein-E (APOE) gene codes for a protein that has a key role in metabolism of cholesterol and triglycerides, with increased levels of apoE found in specific areas of post-mortem schizophrenic brains. This study investigated whether apoE variants influence the prevalence of cardiovascular risk factors (obesity, diabetes and dyslipidaemia), in patients receiving antipsychotic treatment, due to extension of the risk seen in the general population, but also due to the role of the APOE gene in mediating antipsychotic-induced side effects. Seven polymorphisms (rs741780, rs483082, rs429358, rs7412, rs10119, rs439401 and rs405509) were genotyped in 427 American Caucasian patients who were either receiving, or had been prescribed risperidone. Our results support the hypothesis that APOE gene variants influence the prevalence of diabetes and possibly overweight in psychiatric patients. Unfortunately, due to the cross sectional nature of this study, the contribution of antipsychotic treatment was not determined. These associations warrant prospective study to assess interaction between APOE gene variants and the propensity of antipsychotics to induce cardiovascular risk factors.

Keywords

APOECardiovascular diseaseObesityAntipsychoticsSchizophrenia
Type
Original article
Information
European Psychiatry , Volume 24 , Issue 7 , October 2009 , pp. 456 - 463
Copyright
Copyright © Elsevier Masson SAS 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 2004;27:596–601CrossRefGoogle Scholar
Arranz, MJde Leon, JPharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research. Mol Psychiatry 2007;12:707–747CrossRefGoogle Scholar
Bennet, AMDi Angelantonio, EYe, ZWensley, FDahlin, AAhlbom, Aet al.Association of apolipoprotein E genotypes with lipid levels and coronary risk. JAMA 2007;298:1300–1311CrossRefGoogle ScholarPubMed
de Leon, JSusce, MTPan, RMKoch, WHWedlund, PJPolymorphic variations in GSTM1, GSTT1, PgP, CYP2D6, CYP3A5, and dopamine D2 and D3 receptors and their association with tardive dyskinesia in severe mental illness. J Clin Psychopharmacol 2005;25:448–456CrossRefGoogle ScholarPubMed
Dean, BLaws, SMHone, ETaddei, KScarr, EThomas, EAet al.Increased levels of apolipoprotein E in the frontal cortex of subjects with schizophrenia. Biol Psychiatry 2003;54:616–622CrossRefGoogle ScholarPubMed
Digney, AKeriakous, DScarr, EThomas, EDean, BDifferential changes in apolipoprotein E in schizophrenia and bipolar I disorder. Biol Psychiatry 2005;57:711–715CrossRefGoogle ScholarPubMed
Eichner, JEDunn, STPerveen, GThompson, DMStewart, KEStroehla, BCApolipoprotein E polymorphism and cardiovascular disease: a HuGE review. Am J Epidemiol 2002;155:487–495CrossRefGoogle ScholarPubMed
Gottlieb, DJDeStefano, ALFoley, DJMignot, ERedline, SGivelber, RJet al.Apo-E epsilon4 is associated with obstructive sleep apnea/hypopnea: the Sleep Heart Health Study. Neurology 2004;63:664–668CrossRefGoogle ScholarPubMed
Halford, JMazeika, GSlifer, SSpeer, MSaunders, AMStrittmatter, WJet al.Apo-E2 allele increased in tardive dyskinesia. Mov Disord 2006;21:540–542CrossRefGoogle ScholarPubMed
Hong, CJYu, YWLin, CHSong, HLLai, HCYang, KHet al.Association study of apolipoprotein E epsilon4 with clinical phenotype and clozapine response in schizophrenia. Neuropsychobiology 2000; 172–174CrossRefGoogle Scholar
Kalina, ASzalai, CProhaszka, ZReiber, ICsaszar, AAssociation of plasma lipid levels with apolipoprotein E polymorphism in Type 2 diabetes. Diabetes Res Clin Pract 2002;56:63–68CrossRefGoogle ScholarPubMed
Kampman, OAnttila, SIlli, AMattila, KMRontu, RLeinonen, Eet al.Apolipoprotein E polymorphism is associated with age of onset in schizophrenia. J Hum Genet 2004;49:355–359CrossRefGoogle Scholar
Long, JRLiu, PYLiu, YJLu, YXiong, DHElze, Let al.Apo-E and TGF-beta1 genes are associated with obesity phenotypes. J Med Genet 2003;40:918–924CrossRefGoogle ScholarPubMed
Mahley, RWRall, SC Jr.Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet 2000;1:507–537CrossRefGoogle ScholarPubMed
Martins, IJHone, EFoster, JKSunram-Lea, SIGnjec, AFuller, SJet al.Apolipoprotein E, cholesterol metabolism, diabetes, and the convergence of risk factors for Alzheimer's disease and cardiovascular disease. Mol Psychiatry 2006;11:721–736CrossRefGoogle ScholarPubMed
Newcomer, JWAntipsychotic medications: metabolic and cardiovascular risk. J Clin Psychiatry 2007;68(Suppl. 4):8–13Google ScholarPubMed
Nieminen, TKahonen, MViiri, LEGronroos, PLehtimaki, TPharmacogenetics of apolipoprotein E gene during lipid-lowering therapy: lipid levels and prevention of coronary heart disease. Pharmacogenomics 2008;9:1475–1486CrossRefGoogle ScholarPubMed
Osby, UCorreia, NBrandt, LEkbom, ASparen, PMortality and causes of death in schizophrenia in Stockholm county. Sweden. Schizophr Res 2000;45:21–28CrossRefGoogle ScholarPubMed
Profenno, LAFaraone, SVDiabetes and overweight associate with non-Apo-E4 genotype in an Alzheimer's disease population. Am J Med Genet B Neuropsychiatr Genet 2008;147B:822–829CrossRefGoogle Scholar
Purcell, SNeale, BTodd-Brown, KThomas, LFerreira, MABender, Det al.PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007;81:559–575CrossRefGoogle ScholarPubMed
Rankinen, TZuberi, AChagnon, YCWeisnagel, SJArgyropoulos, GWalts, Bet al.The human obesity gene map: the 2005 update. Obesity (Silver Spring, Md.) 2006;14:529–644CrossRefGoogle ScholarPubMed
Schneider, WJKovanen, PTBrown, MSGoldstein, JLUtermann, GWeber, Wet al.Familial dysbetalipoproteinemia. Abnormal binding of mutant apoprotein E to low density lipoprotein receptors of human fibroblasts and membranes from liver and adrenal of rats, rabbits, and cows. J Clin Invest 1981;68:1075–1085CrossRefGoogle ScholarPubMed
Song, YStampfer, MJLiu, SMeta-analysis: apolipoprotein E genotypes and risk for coronary heart disease. Ann Intern Med 2004;141:137–147CrossRefGoogle ScholarPubMed
Susce, MTVillanueva, NDiaz, FJde Leon, JObesity and associated complications in patients with severe mental illnesses: a cross-sectional survey. J Clin Psychiatry 2005;66:167–173CrossRefGoogle ScholarPubMed
Tang, MDai, YHuang, YCai, XTian, XTu, ZThe univariation and multiple linear regression analyses for seventeen SNPs in thirteen cardiovascular disease-predisposing genes and blood pressure in Chinese Han males. Clin Exp Hypertens 2008;30:648–661CrossRefGoogle ScholarPubMed
Weisgraber, KHInnerarity, TLMahley, RWAbnormal lipoprotein receptor-binding activity of the human E apoprotein due to cysteine-arginine interchange at a single site. J Biol Chem 1982;257:2518–2521Google Scholar
Xu, MQSt Clair, DHe, LMeta-analysis of association between Apo-E epsilon4 allele and schizophrenia. Schizophr Res 2006;84:228–235CrossRefGoogle Scholar
Yu, CESeltman, HPeskind, ERGalloway, NZhou, PXRosenthal, Eet al.Comprehensive analysis of Apo-E and selected proximate markers for late-onset Alzheimer's disease: patterns of linkage disequilibrium and disease/marker association. Genomics 2007;89:655–665CrossRefGoogle ScholarPubMed
Submit a response

Comments

No Comments have been published for this article.