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Catechol-O-methyltransferase gene promoter methylation as a peripheral biomarker in male schizophrenia

  • S. Gao (a1), J. Cheng (a1), G. Li (a1), T. Sun (a2), Y. Xu (a1), Y. Wang (a1), X. Du (a1), G. Xu (a2) and S. Duan (a2)...

Abstract

As an epigenetic modification, DNA methylation may reflect the interaction between genetic and environmental factors in the development of schizophrenia (SCZ). Catechol-O-methyltransferase (COMT) gene is a promising candidate gene of SCZ. In the present study, we investigate the association of COMT methylation with the risk of SCZ using bisulfite pyrosequencing technology. Significant association between DNA methylation of COMT and the risk of SCZ is identified (P = 1.618e−007). A breakdown analysis by gender shows that the significance is driven by males (P = 3.310e−009), but not by females. DNA methylation of COMT is not significantly associated with SCZ clinical phenotypes, including p300 and cysteine level. No interaction is found between COMT genotypes and the percent methylation of this gene. Receiver operating characteristic (ROC) curve shows that DNA methylation of COMT is able to predict the SCZ risk in males (area under curve [AUC] = 0.802, P = 1.91e−007). The current study indicates the clinical value of COMT methylation as a potential male-specific biomarker in SCZ diagnosis.

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Corresponding author

* Corresponding author. Tel.:/fax: +86 592 2292579.
** Corresponding author. Tel.:/fax: +86 574 87609950. E-mail addresses:drchengjia@163.com, duanshiwei@nbu.edu.cn

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1

SG, JC and GL are co-first authors of this work.

2

Present address: Zhongshan Hospital, Xiamen University, Xiamen, 361004, China.

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References

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[1]Saha, SChant, DWelham, JMcGrath, JA systematic review of the prevalence of schizophrenia. Plos Med 2005;2:e141.
[2]Gao, SHu, ZCheng, JZhou, WXu, YXie, S, et al.Impact of catechol-O-methyltransferase polymorphisms on risperidone treatment for schizophrenia and its potential clinical significance. Clin Biochem 2012; 45: 787792.
[3]Cheng, JWang, YZhou, KWang, LLi, JZhuang, Q, et al.Male-specific association between dopamine receptor D4 gene methylation and schizophrenia. Plos One 2014;9:e89128.
[4]Lindamer, LALohr, JBHarris, MJJeste, DVGender, estrogen, and schizophrenia. Psychopharmacol Bull 1997; 33: 221228.
[5]Goldstein, JMCherkerzian, STsuang, MTPetryshen, TLSex differences in the genetic risk for schizophrenia: history of the evidence for sex-specific and sex-dependent effects. Am J Med Genet A 2013;162B:698710.
[6]Abel, KMDrake, RGoldstein, JMSex differences in schizophrenia. Int Rev Psychiatry 2010; 22: 417428.
[7]Meyer-Lindenberg, AKohn, PDKolachana, BKippenhan, SMcInerney-Leo, ANussbaum, R, et al.Midbrain dopamine and prefrontal function in humans: interaction and modulation by COMT genotype. Nat Neurosci 2005; 8: 594596.
[8]Walton, ELiu, JHass, JWhite, TScholz, MRoessner, V, et al.MB-COMT promoter DNA methylation is associated with working-memory processing in schizophrenia patients and healthy controls. Epigenetics 2014; 9: 11011107.
[9]Swift-Scanlan, TSmith, CTBardowell, SABoettiger, CAComprehensive interrogation of CpG island methylation in the gene encoding COMT, a key estrogen and catecholamine regulator. BMC Med Genom 2014;7:5.
[10]Dempster, ELMill, JCraig, IWCollier, DAThe quantification of COMT mRNA in post mortem cerebellum tissue: diagnosis, genotype, methylation and expression. BMC Med Genet 2006;7:10.
[11]Nestler, EJPena, CJKundakovic, MMitchell, AAkbarian, SEpigenetic basis of mental illness. Neuroscientist 2016; 22(5): 447463.
[12]Nishioka, MBundo, MKasai, KIwamoto, KDNA methylation in schizophrenia: progress and challenges of epigenetic studies. Genome Med 2012; 4(12): 96
[13]Dai, DCheng, JZhou, KLv, YZhuang, QZheng, R, et al.Significant association between DRD3 gene body methylation and schizophrenia. Psychiatr Res 2014; 220: 772777.
[14]Lott, SABurghardt, PRBurghardt, KJBly, MJGrove, TBEllingrod, VLThe influence of metabolic syndrome, physical activity and genotype on catechol-O-methyl transferase promoter-region methylation in schizophrenia. Pharmacogenomics J 2013; 13: 264271.
[15]Nohesara, SGhadirivasfi, MMostafavi, SEskandari, MRAhmadkhaniha, HThiagalingam, S, et al.DNA hypomethylation of MB-COMT promoter in the DNA derived from saliva in schizophrenia and bipolar disorder. J Psychiatr Res 2011; 45: 14321438.
[16]Abdolmaleky, HMCheng, KHFaraone, SVWilcox, MGlatt, SJGao, F, et al.Hypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and bipolar disorder. Hum Mol Genet 2006; 15: 31323145.
[17]Smith, ARSmith, RGCondliffe, DHannon, ESchalkwyk, LMill, J, et al.Increased DNA methylation near TREM2 is consistently seen in the superior temporal gyrus in Alzheimer's disease brain. Neurobiol Aging 2016; 47: 3540.
[18]Zhou, JHuang, YHuang, RSWang, FXu, LLe, Y, et al.A case-control study provides evidence of association for a common SNP rs974819 in PDGFD to coronary heart disease and suggests a sex-dependent effect. Thromb Res 2012; 130: 602606.
[19]Bachtiar, ISantoso, JMAtmanegara, BGani, RAHasan, ILesmana, LA, et al.Combination of alpha-1-acid glycoprotein and alpha-fetoprotein as an improved diagnostic tool for hepatocellular carcinoma. Clin Chim Acta 2009; 399: 97101.
[20]Zhou, HGuo, JMLou, YRZhang, XJZhong, FDJiang, Z, et al.Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using microRNA as a marker. J Mol Med 2010; 88: 709717.
[21]Liao, QWang, YCheng, JDai, DZhou, XZhang, Y, et al.DNA methylation patterns of protein coding genes and long noncoding RNAs in female schizophrenic patients. Eur J Med Genet 2015; 58: 95104.
[22]Liao, QWang, YCheng, JDai, DZhou, XZhang, Y, et al.DNA methylation patterns of protein-coding genes and long non-coding RNAs in males with schizophrenia. Mol Med Rep 2015
[23]Kinoshita, MNumata, STajima, AShimodera, SOno, SImamura, A, et al.DNA methylation signatures of peripheral leukocytes in schizophrenia. Neuromol Med 2013; 15: 95101.
[24]Xu, QMa, JZPayne, TJLi, MDDetermination of methylated CpG sites in the promoter region of catechol-O-methyltransferase (COMT) and their involvement in the etiology of tobacco smoking. Front Psychiatr 2010;1:16.
[25]Murphy, BCO’Reilly, RLSingh, SMSite-specific cytosine methylation in S-COMT promoter in 31 brain regions with implications for studies involving schizophrenia. Am J Med Genet A 2005;133B:3742.
[26]Mill, JTang, TKaminsky, ZKhare, TYazdanpanah, SBouchard, L, et al.Epigenomic profiling reveals DNA-methylation changes associated with major psychosis. Am J Hum Genet 2008; 82: 696711.
[27]Melas, PARogdaki, MOsby, USchalling, MLavebratt, CEkstrom, TJEpigenetic aberrations in leukocytes of patients with schizophrenia: association of global DNA methylation with antipsychotic drug treatment and disease onset. FASEB J 2012; 26: 27122718.
[28]Mellios, NGaldzicka, MGinns, EBaker, SPRogaev, EXu, J, et al.Gender-specific reduction of estrogen-sensitive small RNA, miR-30b, in subjects with schizophrenia. Schizophr Bull 2012; 38: 433443.
[29]Lai, CYYu, SLHsieh, MHChen, CHChen, HYWen, CC, et al.MicroRNA expression aberration as potential peripheral blood biomarkers for schizophrenia. Plos One 2011;6:e21635.
[30]Kinoshita, MNumata, STajima, AShimodera, SImoto, IOhmori, TPlasma total homocysteine is associated with DNA methylation in patients with schizophrenia. Epigenetics 2013; 8: 584590.
[31]Guidotti, AAuta, JChen, YDavis, JMDong, EGavin, DP, et al.Epigenetic GABAergic targets in schizophrenia and bipolar disorder. Neuropharmacology 2011; 60: 10071016.
[32]Ernst, JKheradpour, PMikkelsen, TSShoresh, NWard, LDEpstein, CB, et al.Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 2011; 473: 4349.
[33]Gerstein, MBKundaje, AHariharan, MLandt, SGYan, KKCheng, C, et al.Architecture of the human regulatory network derived from ENCODE data. Nature 2012; 489: 91100.

Keywords

Catechol-O-methyltransferase gene promoter methylation as a peripheral biomarker in male schizophrenia

  • S. Gao (a1), J. Cheng (a1), G. Li (a1), T. Sun (a2), Y. Xu (a1), Y. Wang (a1), X. Du (a1), G. Xu (a2) and S. Duan (a2)...

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Catechol-O-methyltransferase gene promoter methylation as a peripheral biomarker in male schizophrenia

  • S. Gao (a1), J. Cheng (a1), G. Li (a1), T. Sun (a2), Y. Xu (a1), Y. Wang (a1), X. Du (a1), G. Xu (a2) and S. Duan (a2)...
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