Metabolic syndrome in patients taking clozapine: prevalence and influence of catechol-O-methyltransferase genotype
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- 作者：Yi Zhang (1)
Meijuan Chen (1)
Jun Chen (2)
Zhiguo Wu (2)
Shunying Yu (3)
Yiru Fang (2)
Chen Zhang (1) (4) - 关键词：Clozapine ; COMT ; Metabolic syndrome ; Triglyceride ; Association
- 刊名：Psychopharmacology
- 出版年：2014
- 出版时间：May 2014
- 年：2014
- 卷：231
- 期：10
- 页码：2211-2218
- 全文大小：
- 参考文献：1. Alberti KG, Zimmet P, Shaw J (2005) The metabolic syndrome—a new worldwide definition. Lancet 366:1059-062 CrossRef
2. Araki A, Sako Y (1987) Determination of free and total homocysteine in human plasma by high-performance liquid chromatography with fluorescence detection. J Chromatogr 422:43-2 CrossRef
3. Asenjo Lobos C, Komossa K, Rummel-Kluge C, Hunger H, Schmid F, Schwarz S, Leucht S (2010) Clozapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev: CD006633
4. Backhed F (2009) Changes in intestinal microflora in obesity: cause or consequence? J Pediatr Gastroenterol Nutr 48(Suppl 2):S56–S57 CrossRef
5. Bao YQ, Lu JX, Wang C, Yang M, Li HT, Zhang XY, Zhu JH, Lu HJ, Jia WP, Xiang KS (2008) Optimal waist circumference cutoffs for abdominal obesity in Chinese. Atherosclerosis 201:378-84 CrossRef
6. Bialecka M, Kurzawski M, Roszmann A, Robowski P, Sitek EJ, Honczarenko K, Gorzkowska A, Budrewicz S, Mak M, Jarosz M, Golab-Janowska M, Koziorowska-Gawron E, Drozdzik M, Slawek J (2012) Association of COMT, MTHFR, and SLC19A1(RFC-1) polymorphisms with homocysteine blood levels and cognitive impairment in Parkinson's disease. Pharmacogenet Genomics 22:716-24 CrossRef
7. Burghardt KJ, Pilsner JR, Bly MJ, Ellingrod VL (2012) DNA methylation in schizophrenia subjects: gender and MTHFR 677C/T genotype differences. Epigenomics 4:261-68 CrossRef
8. Cai J, Zhang W, Yi Z, Lu W, Wu Z, Chen J, Yu S, Fang Y, Zhang C (2013) Influence of polymorphisms in genes SLC1A1, GRIN2B, and GRIK2 on clozapine-induced obsessive-compulsive symptoms. Psychopharmacology (Berl) 230:49-5 CrossRef
9. Chen J, Lipska BK, Halim N, Ma QD, Matsumoto M, Melhem S, Kolachana BS, Hyde TM, Herman MM, Apud J, Egan MF, Kleinman JE, Weinberger DR (2004) Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. Am J Hum Genet 75:807-21 CrossRef
10. Clarke R, Collins R, Lewington S, Donald A, Alfthan G, Tuomilehto J, Arnesen E, Bonaa K, Blacher J, Boers GHJ, Bostom A, Bots ML, Grobee DE, Brattstrom L, Breteler MMB, Hofman A, Chambers JC, Kooner JS, Coull BM, Evans RW, Kuller LH, Evers S, Folsom AR, Freyburger G, Parrot F, Genst J, Dalery K, Graham IM, Daly L, Hoogeveen EK, Kostense PJ, Stehouwer CDA, Hopknis PN, Jacques P, Selhub J, Luft FC, Jungers P, Lindgren A, Lolin YI, Loehrer F, Fowler B, Mansoor MA, Malinow MR, Ducimetiere P, Nygard O, Refsum H, Vollset SE, Ueland PM, Omenn GS, Beresford SAA, Roseman JM, Parving HH, Gall MA, Perry IJ, Ebraham SB, Shaper AG, Robinson K, Jacobsen DW, Schwartz SM, Siscovick DS, Stampfer MJ, Henekens CH, Feskens EJM, Kromhout D, Ubbink J, Elwood P, Pickering J, Verhoef P, von Eckardstein A, Schulte H, Assmann G, Wald N, Law MR, Whincup PH, Wilcken DEL, Sherliker P, Linksted P, Smith GD, Witteman JCM, Israelsson B, Sexton G, Wu LL, Joubran R, Norrving B, Hultberg B, Andersson A, Johansson BB, Bergmark C, Svardal AM, Evans AE, Pancharuniti N, Lewis CA, Holman R, Stratton I, Johnston C, Morris J, Collaboration HS (2002) Homocysteine and risk of ischemic heart disease and stroke—a meta-analysis. JAMA 288:2015-022 CrossRef
11. Comasco E, Hellgren C, Sundstrom-Poromaa I (2012) Influence of catechol-O-methyltransferase Val158Met polymorphism on startle response in the presence of high estradiol levels. Eur Neuropsychopharmacol 23:629-35 CrossRef
12. Davey KJ, O'Mahony SM, Schellekens H, O'Sullivan O, Bienenstock J, Cotter PD, Dinan TG, Cryan JF (2012) Gender-dependent consequences of chronic olanzapine in the rat: effects on body weight, inflammatory, metabolic and microbiota parameters. Psychopharmacology (Berl) 221:155-69 CrossRef
13. De Hert M, Schreurs V, Sweers K, Van Eyck D, Hanssens L, Sinko S, Wampers M, Scheen A, Peuskens J, van Winkel R (2008) Typical and atypical antipsychotics differentially affect long-term incidence rates of the metabolic syndrome in first-episode patients with schizophrenia: a retrospective chart review. Schizophr Res 101:295-03 CrossRef
14. Ellingrod VL, Miller DD, Taylor SF, Moline J, Holman T, Kerr J (2008) Metabolic syndrome and insulin resistance in schizophrenia patients receiving antipsychotics genotyped for the methylenetetrahydrofolate reductase (MTHFR) 677C/T and 1298A/C variants. Schizophr Res 98:47-4 CrossRef
15. Falchi M, Wilson SG, Paximadas D, Swaminathan R, Spector TD (2008) Quantitative linkage analysis for pancreatic B-cell function and insulin resistance in a large twin cohort. Diabetes 57:1120-124 CrossRef
16. Fatemi SH, Folsom TD (2007) Catechol-O-methyltransferase gene regulation in rat frontal cortex. Mol Psychiatry 12:322-23 CrossRef
17. Fatemi SH, Folsom TD, Reutiman TJ, Novak J, Engel RH (2012) Comparative gene expression study of the chronic exposure to clozapine and haloperidol in rat frontal cortex. Schizophr Res 134:211-18 CrossRef
18. Gao S, Hu Z, Cheng J, Zhou W, Xu Y, Xie S, Liu S, Li Z, Guo J, Dong J, Huang M (2012) Impact of catechol-o-methyltransferase polymorphisms on risperidone treatment for schizophrenia and its potential clinical significance. Clin Biochem 45:787-92 CrossRef
19. Gellekink H, Muntjewerff JW, Vermeulen SHHM, Hermus ARMM, Blom HJ, den Heijer M (2007) Catechol-O-methyltransferase genotype is associated with plasma total homocysteine levels and may increase venous thrombosis risk. Thromb Haemost 98:1226-231
20. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC, Spertus JA, Costa F (2005) Diagnosis and management of the metabolic syndrome—an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation 112:2735-752 CrossRef
21. Gupta M, Bhatnagar P, Grover S, Kaur H, Baghel R, Bhasin Y, Chauhan C, Verma B, Manduva V, Mukherjee O, Purushottam M, Sharma A, Jain S, Brahmachari SK, Kukreti R (2009) Association studies of catechol-O-methyltransferase (COMT) gene with schizophrenia and response to antipsychotic treatment. Pharmacogenomics 10:385-97 CrossRef
22. Guven A, Inanc F, Kilinc M, Ekerbicer H (2005) Plasma homocysteine and lipoprotein (a) levels in Turkish patients with metabolic syndrome. Heart Vessels 20:290-95 CrossRef
23. Hajer GR, van der Graaf Y, Olijhoek JK, Verhaar MC, Visseren FL (2007) Levels of homocysteine are increased in metabolic syndrome patients but are not associated with an increased cardiovascular risk, in contrast to patients without the metabolic syndrome. Heart 93:216-20 CrossRef
24. Hu S, Yao M, Peterson BS, Xu D, Hu J, Tang J, Fan B, Liao Z, Yuan T, Li Y, Yue W, Wei N, Zhou W, Huang M, Xu Y (2013) A randomized, 12-week study of the effects of extended-release paliperidone (paliperidone ER) and olanzapine on metabolic profile, weight, insulin resistance, and beta-cell function in schizophrenic patients. Psychopharmacology (Berl) 230:3-3 CrossRef
25. Jassim G, Skrede S, Vazquez MJ, Wergedal H, Vik-Mo AO, Lunder N, Dieguez C, Vidal-Puig A, Berge RK, Lopez M, Steen VM, Ferno J (2012) Acute effects of orexigenic antipsychotic drugs on lipid and carbohydrate metabolism in rat. Psychopharmacology (Berl) 219:783-94 CrossRef
26. Lamberti P, Zoccolella S, Iliceto G, Armenise E, Fraddosio A, de Mari M, Livrea P (2005) Effects of levodopa and COMT inhibitors on plasma homocysteine in Parkinson's disease patients. Mov Disord 20:69-2 CrossRef
27. Lott SA, Burghardt PR, Burghardt KJ, Bly MJ, Grove TB, Ellingrod VL (2013) The influence of metabolic syndrome, physical activity and genotype on catechol-O-methyl transferase promoter-region methylation in schizophrenia. Pharmacogenomics J 13:264-71 CrossRef
28. McEvoy JP, Meyer JM, Goff DC, Nasrallah HA, Davis SM, Sullivan L, Meltzer HY, Hsiao J, Scott Stroup T, Lieberman JA (2005) 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 80:19-2 CrossRef
29. McEvoy JP, Lieberman JA, Stroup TS, Davis SM, Meltzer HY, Rosenheck RA, Swartz MS, Perkins DO, Keefe RS, Davis CE, Severe J, Hsiao JK (2006) Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry 163:600-10 CrossRef
30. Mitchell AJ, Vancampfort D, Sweers K, van Winkel R, Yu W, De Hert M (2013) Prevalence of metabolic syndrome and metabolic abnormalities in schizophrenia and related disorders—a systematic review and meta-analysis. Schizophr Bull 39:306-18 CrossRef
31. Monneret D, Tamisier R, Ducros V, Garrel C, Levy P, Baguet JP, Faure P, Pepin JL (2012) The impact of obstructive sleep apnea on homocysteine and carotid remodeling in metabolic syndrome. Respir Physiol Neurobiol 180:298-04 CrossRef
32. Muller T (2008) Role of homocysteine in the treatment of Parkinson's disease. Expert Rev Neurother 8:957-67 CrossRef
33. Nissinen E, Nissinen H, Larjonmaa H, Vaananen A, Helkamaa T, Reenila I, Rauhala P (2005) The COMT inhibitor, entacapone, reduces levodopa-induced elevations in plasma homocysteine in healthy adult rats. J Neural Transm 112:1213-221 CrossRef
34. Nygard O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE (1997) Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med 337:230-36 CrossRef
35. Ou JJ, Xu Y, Chen HH, Fan X, Gao K, Wang J, Guo XF, Wu RR, Zhao JP (2013) Comparison of metabolic effects of ziprasidone versus olanzapine treatment in patients with first-episode schizophrenia. Psychopharmacology (Berl) 225:627-35 CrossRef
36. Papaleo F, Erickson L, Liu G, Chen J, Weinberger DR (2012) Effects of sex and COMT genotype on environmentally modulated cognitive control in mice. Proc Natl Acad Sci U S A 109:20160-0165 CrossRef
37. Reaven GM (1988) Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37:1595-607 CrossRef
38. Ryu S, Oh S, Cho EY, Nam HJ, Yoo JH, Park T, Joo YH, Kwon JS, Hong KS (2011) Interaction between genetic variants of DLGAP3 and SLC1A1 affecting the risk of atypical antipsychotics-induced obsessive-compulsive symptoms. Am J Med Genet Part B Neuropsychiatr Genet 156B:949-59 CrossRef
39. Shi YY, He L (2005) SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res 15:97-8 CrossRef
40. Shield AJ, Thomae BA, Eckloff BW, Wieben ED, Weinshilboum RM (2004) Human catechol O-methyltransferase genetic variation: gene resequencing and functional characterization of variant allozymes. Mol Psychiatry 9:151-60 CrossRef
41. Tenorio-Laranga J, Mannisto PT, Karayiorgou M, Gogos JA, Garcia-Horsman JA (2009) Sex-dependent compensated oxidative stress in the mouse liver upon deletion of catechol O-methyltransferase. Biochem Pharmacol 77:1541-552 CrossRef
42. van Winkel R, Rutten BP, Peerbooms O, Peuskens J, van Os J, De Hert M (2010) MTHFR and risk of metabolic syndrome in patients with schizophrenia. Schizophr Res 121:193-98 CrossRef
43. Vaya A, Rivera L, Hernandez-Mijares A, de la Fuente M, Sola E, Romagnoli M, Alis R, Laiz B (2012) Homocysteine levels in morbidly obese patients: its association with waist circumference and insulin resistance. Clin Hemorheol Microcirc 52:49-6
44. Voutilainen S, Tuomainen TP, Korhonen M, Mursu J, Virtanen JK, Happonen P, Alfthan G, Erlund I, North KE, Mosher MJ, Kauhanen J, Tiihonen J, Kaplan GA, Salonen JT (2007) Functional COMT Val158Met polymorphism, risk of acute coronary events and serum homocysteine: the Kuopio ischaemic heart disease risk factor study. PLoS One 2:e181 CrossRef
45. Wu RR, Zhao JP, Liu ZN, Zhai JG, Guo XF, Guo WB, Tang JS (2006) Effects of typical and atypical antipsychotics on glucose-insulin homeostasis and lipid metabolism in first-episode schizophrenia. Psychopharmacology (Berl) 186:572-78 CrossRef
46. Yan H, Chen JD, Zheng XY (2013) Potential mechanisms of atypical antipsychotic-induced hypertriglyceridemia. Psychopharmacology (Berl) 229:1- CrossRef
47. Yi ZH, Zhang C, Wu ZG, Hong W, Li ZZ, Fang YR, Yu SY (2011) Lack of effect of brain derived neurotrophic factor (BDNF) Val66Met polymorphism on early onset schizophrenia in Chinese Han population. Brain Res 1417:146-50 CrossRef
48. Zarkesh M, Faam B, Daneshpour MS, Azizi F, Hedayati M (2012) The relationship between metabolic syndrome, cardiometabolic risk factors and inflammatory markers in a Tehranian population: the Tehran lipid and glucose study. Intern Med 51:3329-335
49. Zhang JP, Malhotra AK (2011) Pharmacogenetics and antipsychotics: therapeutic efficacy and side effects prediction. Expert Opin Drug Metab Toxicol 7:9-7 CrossRef
50. Zhang C, Fang YR, Xie B, Cheng WH, Du YS, Wang DX, Yu SY (2010) No genetic association between dopamine D1 receptor gene and [early onset] schizophrenia. Psychiatry Res 177:350-53 CrossRef
51. Zhang C, Li ZZ, Shao Y, Xie B, Du YS, Fang YR, Yu SY (2011) Association study of tryptophan hydroxylase-2 gene in schizophrenia and its clinical features in Chinese Han population. J Mol Neurosci 43:406-11 CrossRef
52. Zhang Y, Chen M, Wu Z, Chen J, Yu S, Fang Y, Zhang C (2013) Association study of Val66Met polymorphism in brain-derived neurotrophic factor gene with clozapine-induced metabolic syndrome: preliminary results. PLoS One 8:e72652 CrossRef
53. Zhou H, Guo ZR, Yu LG, Hu XS, Xu BH, Liu HB, Wu M, Zhou ZY (2010) Evidence on the applicability of the ATPIII, IDF and CDS metabolic syndrome diagnostic criteria to identify CVD and T2DM in the Chinese population from a 6.3-year cohort study in mid-eastern China. Diabetes Res Clin Pract 90:319-25 CrossRef
54. Zoccolella S, Iliceto G, deMari M, Livrea P, Lamberti P (2007) Management of L-Dopa related hyperhomocysteinemia: catechol-O-methyltransferase (COMT) inhibitors or B vitamins? Results from a review. Clin Chem Lab Med 45:1607-613 CrossRef - 作者单位：Yi Zhang (1)
Meijuan Chen (1)
Jun Chen (2)
Zhiguo Wu (2)
Shunying Yu (3)
Yiru Fang (2)
Chen Zhang (1) (4)
1. Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai, 200030, China
2. Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China
3. Department of Genetics, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China
4. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, 650223, Yunnan, China - ISSN：1432-2072
文摘
Rationale Metabolic syndrome (MetS) has consistently been identified as an adverse effect of long-term treatment with atypical antipsychotics (AAPs) such as clozapine. Elevated serum homocysteine concentration has been found to act as an independent risk factor for MetS, and catechol-O-methyltransferase (COMT) catalyzes the homocysteine metabolism. We accordingly hypothesized that COMT dysregulation may confer the susceptibility to MetS induced by AAPs, potentially in a gender-specific manner, because the interaction effects of COMT and gender have been consistently reported. Objectives This study aimed at determining the prevalence and influence of COMT on MetS among a population undergoing long-term clozapine treatment. Methods A total of 468 schizophrenia patients taking clozapine were divided into two groups, those experiencing MetS and non-MetS. We genotyped three functional variants (rs4633, rs4680, and rs4818) in COMT and measured the serum levels of fasting homocysteine, glucose, triglyceride (TG), and high-density lipoprotein cholesterol. Results MetS was found in 202/468 (43.2?%) of all the patients, with 40.2?% prevalence (138/343) in males and 51.2?% (64/125) in females. Patients with MetS had notably higher metabolic parameters than those without MetS. The mean levels of homocysteine in patients with MetS were significantly higher than those without MetS. We found a positive association between the rs4680 polymorphism and the serum triglyceride levels (corrected P--.024). Further analysis revealed that the rs4680 Met allele was significantly associated with increased triglyceride levels among female patients (P--.009), but not among males (P--.07). Conclusions Our findings suggest a potential association between rs4680 in COMT and elevated TG levels, particularly among female patients.