Advanced search
Publication Cover
Pharmacogenomics Volume 15, 2014 - Issue 4
Submit an article Journal homepage
210
Views
0
CrossRef citations to date
0
Altmetric
Research Article

Association of FTO, LEPR and MTHFR Gene Polymorphisms with Metabolic Syndrome in Schizophrenia Patients Receiving Antipsychotics

Siti Norsyuhada Roffeei1 Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, MalaysiaCorrespondence[email protected]
View further author information
,
Zahurin Mohamed1 Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, MalaysiaView further author information
,
Gavin P Reynolds2 Biomedical Research Centre, Sheffield Hallam University, Sheffield, UK.View further author information
,
Mas Ayu Said1 Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, MalaysiaView further author information
,
Ahmad Hatim4 Department of Psychological Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, MalaysiaView further author information
,
Elsa Haniffah Mejia Mohamed1 Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, MalaysiaView further author information
,
Syarinaz Ahmad Aida4 Department of Psychological Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, MalaysiaView further author information
&
Nor Zuraida Zainal4 Department of Psychological Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, MalaysiaView further author information
 show all
Pages 477-485 | Published online: 13 Mar 2014

References

  • Weiden PJ , MackellJA, McDonnellDD. Obesity as a risk factor for antipsychotic noncompliance. Schizophr. Res.66 , 51–57 (2004).
  • Kang SG , LeeHJ, ParkYM et al. Possible association between the -2548A/G polymorphism of the leptin gene and olanzapine-induced weight gain. Prog. Neuropsychopharmacol. Biol. Psychiatry 32(1) , 160–163 (2008).
  • Jassim G , FernoJ, TheisenFM et al. Association study of energy homeostasis genes and antipsychotic-induced weight gain in patients with schizophrenia. Pharmacopsychiatry 44(1) , 15–20 (2011).
  • Gregoor JG , van der Weide J, Mulder H et al. Polymorphisms of the LEP- and LEPR gene and obesity in patients using antipsychotic medication. J. Clin. Psychopharmacol.29 , 21–25 (2009).
  • McEvoy JP , MeyerJM, GoffDC et al. Prevalence of the metabolic syndrome in patients with schizophrenia: baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES III. Schizophr. Res. 80(1) , 19–32 (2005).
  • Saddichha S , ManjunathaN, AmeenS, AkhtarS. Metabolic syndrome in first episode schizophrenia – a randomized double-blind controlled, short-term prospective study. Schizophr. Res.101(1–3) , 266–272 (2008).
  • Bai YM , ChenTT, YangWS et al. Association of adiponectin and metabolic syndrome among patients taking atypical antipsychotics for schizophrenia: a cohort study. Schizophr. Res. 111(1–3) , 1–8 (2009).
  • Huang MC , LuML, TsaiCJ et al. Prevalence of metabolic syndrome among patients with schizophrenia or schizoaffective disorder in Taiwan. Acta Psychiatr. Scand. 120(4) , 274–280 (2009).
  • Sugawara N , Yasui-FurukoriN, SatoY et al. Prevalence of metabolic syndrome among patients with schizophrenia in Japan. Schizophr. Res. 123(2–3) , 244–250 (2010).
  • Moy FM , BulgibaA. The modified NCEP ATP III criteria maybe better than the IDF criteria in diagnosing Metabolic Syndrome among Malays in Kuala Lumpur. BMC Public Health10 , 678 (2010).
  • Lett TA , WallaceTJ, ChowdhuryNI, TiwariAK, KennedyJL, MullerDJ. Pharmacogenetics of antipsychotic-induced weight gain: review and clinical implications. Mol. Psychiatry17 , 242–266 (2012).
  • Allison DB , MentoreJL, HeoM et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am. J. Psychiatry 156 , 1686–1696 (1999).
  • Reynolds GP , YevtuschenkoOO, GordonS, ArranzB, SanL, CooperSJ. The obesity risk gene FTO influences body mass in chronic schizophrenia but not initial antipsychotic drug-induced weight gain in first-episode patients. Int. J. Neuropsychopharmacol.16(6) , 1421–1425 (2012).
  • Saddichha S , VishnuvardhanG, AkhtarS. Obesity, diabetes and hypertension associated with antipsychotic use in remitted schizophrenia. Int. J. Risk Saf. Med.23(3) , 181–185 (2011).
  • Povel CM , BoerJM, ReilingE, FeskensEJ. Genetic variants and the metabolic syndrome: a systematic review. Obes. Rev.12(11) , 952–967 (2011).
  • De Hert M , SchreursV, VancampfortD, van Winkel R. Metabolic syndrome in people with schizophrenia: a review. World Psychiatry8 , 15–22 (2009).
  • Reynolds GP . Pharmacogenetic aspects of antipsychotic drug-induced weight gain – a critical review. Clin. Psychopharmacol. Neuroscience10(2) , 71–77 (2012).
  • Lane HY , LiuYC, HuangCL et al. Risperidone-related weight gain: genetic and nongenetic predictors. J. Clin. Psychopharmacol. 26 , 128–134 (2006).
  • Templeman LA , ReynoldsGP, ArranzB, SanL. Polymorphisms of the 5-HT2C receptor and leptin genes are associated with antipsychotic drug-induced weight gain in Caucasian subjects with a first-episode psychosis. Pharmacogenet. Genomics15 , 195–200 (2005).
  • Zhang ZJ , YaoZJ, MouXD et al. Association of -2548G/A functional polymorphism in the promoter region of leptin gene with antipsychotic agent-induced weight gain. Zhonghua Yi Xue Za Zhi 83 , 2119–2123 (2003).
  • Wu RR , ZhaoJP, ShaoP, OuJJ, ChangMH. Genetic predictors of antipsychotic-induced weight gain: a case-matched multi-gene study. J. Central South Univ. (Med. Sci.)36(8) , 720–723 (2011).
  • Ellingrod VL , BishopJR, MolineJ, LinYC, MillerDD. Leptin and leptin receptor gene polymorphisms and increases in body mass index (BMI) from olanzapine treatment in persons with schizophrenia. Psychopharmacol. Bull.40(1) , 57–62 (2007).
  • American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, (4th Edition, Text Revision). American Psychiatric Association, Washington, DC, USA (2000).
  • Grundy SM , CleemanJI, DanielsSR et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 112 , 2735–2752 (2005).
  • Perez-Iglesias R , MataI, AmadoJA et al. Effect of FTO, SH2B1, LEP, and LEPR polymorphisms on weight gain associated with antipsychotic treatment. J. Clin. Psychopharmacol. 30 , 661–666 (2010).
  • Frayling TM , TimpsonNJ, WeedonMN et al. A common variant in the FTO gene is asociated with body mass index and predisposes to childhood and adult obesity. Science 316(5826) , 889–894 (2007).
  • Haupt A , ThamerC, MachannJ et al. Impact of variation in the FTO gene on whole body fat distribution, ectopic fat, and weight loss. Obesity (Silver Spring) 16(8) , 1969–1972 (2008).
  • Lappalainen TJ , TolppanenAM, KolehmainenM et al. The common variant in the FTO gene did not modify the effect of lifestyle changes on body weight: the Finnish Diabetes Prevention Study. Obesity (Silver Spring) 17(4) , 832–836 (2009).
  • Tan JT , DorajooR, SeielstadM et al. FTO variants are associated with obesity in the Chinese and Malay populations in Singapore. Diabetes57(10) , 2851–2857 (2008).
  • Yajnik CS , JanipalliCS, BhaskarS et al. FTO gene variants are strongly associated with Type 2 diabetes in south Asian Indians. Diabetologia52(2) , 247–252 (2009).
  • Willer CJ , SpeliotesEK, LoosRJ et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat. Genet. 41 , 25–34 (2009).
  • Liu Y , LiuZ, SongY et al. Meta-analysis added power to identify variants in FTO associated with Type 2 diabetes and obesity in the Asian population. Obesity (Silver Spring) 18(8) , 1619–1624 (2010).
  • Thorleifsson G , WaltersGB, GudbjartssonDF et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat. Genet. 41(1) , 18–24 (2009).
  • Meyre D , DelplanqueJ, ChevreJC et al. Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations. Nat. Genet. 41 , 157–159 (2009).
  • Fawcett KA , BarrosoI. The genetics of obesity: FTO leads the way. Trend Genet.26 , 266–274 (2010).
  • Wang P , YangFJ, DuH et al. Involvement of leptin receptor long isoform (LepRb)-STAT3 signaling pathway in brain fat mass- and obesity-associated (FTO) downregulation during energy restriction. Mol. Med. 17 , 523–532 (2011).
  • Church C , LeeS, BaggEA et al. A mouse model for the metabolic effects of the human fat mass and obesity associated FTO gene. PLoS Genet. 5(8) , e1000599 (2009).
  • Fischer J , KochL, EmmerlingC et al. Inactivation of the FTO gene protects from obesity. Nature 458 , 894–898 (2009).
  • Gregoor JG , van der Weide J, Loovers HM, van Megen HJ, Egberts TC, Heerdink ER. Association between LEP and LEPR gene polymorphisms and dyslipidemia in patients using atypical antipsychotic medication. Psychiatry Genetics20(6) , 311–316 (2010).
  • Salanti G , AmountzaG, NtzaniEE, IoannidisJP. Hardy–Weinberg equilibrium in genetic association studies: an empirical evaluation of reporting, deviations, and power. Eur. J. Hum. Genet.13 , 840–848 (2005).
  • Vilella E , CostasJ, SanjuanJ et al. Association of schizophrenia with DTNBP1 but not with DAO, DAOA, NRG1 and RGS4 nor their genetic interaction. Psychiatric Res. 42 , 278–288 (2008).
  • Packer BR , YeagerM, StaatsB et al. SNP500Cancer: a public resource for sequence validation and assay development for genetic variation in candidate genes. Nucleic Acids Res. 32 , D528–D532 (2004).
  • Snelgrove T , LimS, GreenwoodC et al. Association of Toll-like receptor 4 variants and ankylosing spondylitis: a case–control study. J. Rheumatol. 34 , 368–370 (2007).
  • Ellingrod VL , MillerDD, TaylorSF, MolineJ, HolmanT, KerrJ. Metabolic syndrome and insulin resistance in schizophrenia patients receiving antipsychotics genotyped for the methylenetetrahydrofolate reductase (MTHFR) 677C/T and 1298A/C variants. Schizophr. Res.98 , 47–54 (2008).
  • Devlin AM , NgaiYF, RonsleyR, PanagiotopoulosC. Cardiometabolic risk and the MTHFR C677T variant in children treated with second-generation antipsychotics. Transl. Psychiatry2 , e71 (2012).
  • van Winkel R , RuttenBP, PeerboomsO, PeuskensJ, van Os J, De Hert M. MTHFR and risk of metabolic syndrome in patients with schizophrenia. Schizophr. Res.121 , 193–198 (2010).
  • Adkins DE , AbergK, McClayJL et al. Genomewide pharmacogenomic study of metabolic side effects to antipsychotic drugs. Mol. Psychiatry 16(3) , 321–332 (2011).
  • Jirtle RL , SkinnerMK. Environmental epigenomics and disease susceptibility. Nat. Rev. Genet.8(4) , 253–262 (2007).
  • Axume J , SmithSS, PogribnyIP, MoriartyDJ, CaudillMA. The MTHFR 677TT genotype and folate intake interact to lower global leukocyte DNA methylation in young Mexican American women. Nutr. Res.27(1) , 1365–1317 (2007).
  • Burghardt KJ , PilsnerJR, BlyMJ, EllingrodVL. DNA methylation in schizophrenia subjects: gender and MTHFR 677C/T genotype differences. Epigenomics4(3) , 261–268 (2012).
  • Kim YI . 5,10-methylenetetrahydrofolate reductase polymorphisms and pharmacogenetics: a new role of single nucleotide polymorphisms in the folate metabolic pathway in human health and disease. Nutr. Rev.63 , 398–407 (2005).
  • Toole JF , MalinowMR, ChamblessLE et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 291 , 565–575 (2004).
  • Henderson DC , CopelandPM, BorbaCP et al. Glucose metabolism in patients with schizophrenia treated with olanzapine or quetiapine: a frequently sampled intravenous glucose tolerance test and minimal model analysis. J. Clin. Psychiatry 67 , 789–797 (2006).
  • Terruzzi I , SenesiP, FermoI, LattuadaG, LuziL. Are genetic variants of the methyl group metabolism enzymes risk factors predisposing to obesity? J. Endocrinol. Invest.30(9) , 747–753 (2007).
  • Lewis DA , MoghaddamB. Cognitive dysfunction in schizophrenia: convergence of gamma-aminobutyric acid and glutamate alterations. Arch. Neurol.63 , 1372–1376 (2006).
  • Chen AR , ZhangHG, WangZP. C-reactive protein, vitamin B12 and C677T polymorphism of N-5,10-methylenetetrahydrofolate reductase gene are related to insulin resistance and risk factors for metabolic syndrome in Chinese population. Clin. Invest. Med.33(5) , E290–E297 (2010).
  • Loos RJF , LindgrenCM, LiS et al. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat. Genet. 40(6) , 768–775 (2008).
  • Zeggini E , ScottLJ, SaxenaR et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for Type 2 diabetes. Nat. Genet. 40(5) , 638–645 (2008).
  • Klerk M , VerhoefP, ClarkeR, BlomHJ, KokFJ, Schouten EG; MTHFR Studies Collaboration Group. MTHFR 677C>T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA288 , 2023–2031 (2002).
  • Inamoto N , KatsuyaT, KokuboY et al. Association of methylenetetrahydrofolate reductase gene polymorphism with carotid atherosclerosis depending on smoking status in a Japanese general population. Stroke 34 , 1628–1633 (2003).
  • Benes P , KankovaK, MuzikJ et al. Methylenetetrahydrofolate reductase polymorphism, Type II diabetes, coronary artery disease, and essential hypertension in the Czech population. Mol. Genet. Metab. 73 , 188–195 (2001).
  • Sun J , XuY, ZhuY et al. Genetic polymorphism of methylenetetrahydrofolate reductase as a risk factor for diabetic nephropathy in Chinese Type 2 diabetic patients. Diabetes Res. Clin. Pract. 64(3) , 185–190 (2004).
  • Ueland PM , RefsumH, StablerSP, MalinowMR, AnderssonA, AllenRH. Total homocysteine in plasma and serum: methods and clinical applications. Clin. Biochem.93 , 1764–1779 (1993).
  • Quian X , LuZ, TanM et al. A meta-analysis of association between C677T polymorphism in the methylenetetrahydrofolate reductase gene and hypertension. Eur. J. Hum. Genet. 15(12) , 1239–1245 (2007).
  • Zhang XY , TanYL, ZhouDF et al. Association of clozapine-induced weight gain with a polymorphism in the leptin promoter region in patients with chronic schizophrenia in a Chinese population. J. Clin. Psychopharmacol. 27 , 246–251 (2007).
  • McFarlane SI . Antidiabetic medications and weight gain: implications for the practicing physician. Curr. Diab. Rep.9(3) , 249–254 (2009).
  • Neutel CI , Campbell N; Canadian Hypertension Society. Changes in lifestyle after hypertension diagnosis in Canada. Can. J. Cardio.24(3) , 199–204 (2008).
  • Correll CU , LenczT, MalhotraAK. Antipsychotic drugs and obesity. Trends Mol. Med.17 , 97–107 (2011).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.