title: Hypermethylation of the enolase gene (ENO2) in autism.
abstract: It has been hypothesized that dysregulation of brain-expressed genes is the major predisposing underlying mechanism for autism. This dysregulation may be mediated by differential methylation of CpG sites within gene promoters, which could be candidate biomarkers and used for early clinical screening of autism. A total of 131 pairs of age- and sex-matched autistic and control subjects were recruited in this study. Peripheral blood cells were analyzed. The first five pairs were randomly applied to array-based genome-wide methylation studies. A neuron-specific gene, ENO2, was found to be hypermethylated in the autistic samples. This difference was validated by bisulfite sequencing PCR (BSP). The differential expression of ENO2 gene was further analyzed with RT-qPCR and ELISA. The hypermethylation of ENO2 within the promoter region was confirmed by BSP to be present in 14.5 % (19/131) of the total of the autistic samples. The mean ENO2 RNA level in these 19 autistic samples was reduced by about 70 % relative to that in controls. The average level of ENO2 protein expression in the 19 autistic samples (15.18 ± 3.51 μg/l) was about half of that in the controls (33.86 ± 8.16 μg/l).
  
  
  CONCLUSIONS
  These findings suggest that reduced ENO2 expression may be a biomarker for a subset of autistic children.
authors.affiliation: Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, China, wy_rain@126.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Yudan
authors.initials: Y
authors.lastname: Fang
authors.forename: Fengling
authors.initials: F
authors.lastname: Zhang
authors.forename: Miao
authors.initials: M
authors.lastname: Xu
authors.forename: Jingzhi
authors.initials: J
authors.lastname: Zhang
authors.forename: Jingbin
authors.initials: J
authors.lastname: Yan
authors.forename: Weina
authors.initials: W
authors.lastname: Ju
authors.forename: W Ted
authors.initials: WT
authors.lastname: Brown
authors.forename: Nanbert
authors.initials: N
authors.lastname: Zhong
mesh_terms: D001321:Autistic Disorder / Q000201:enzymology* / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D009154:Mutation; D010751:Phosphopyruvate Hydratase / Q000235:genetics*
chemical_list: D015415:Biomarkers; D010751:Phosphopyruvate Hydratase
references.citation: Childs Nerv Syst. 2010 Feb;26(2):205-13
references.pmid: 19902222
references.citation: Epigenetics. 2011 Apr;6(4):410-5
references.pmid: 21343703
references.citation: Annu Rev Med. 2009;60:367-80
references.pmid: 19630577
references.citation: BMC Psychiatry. 2009 Apr 30;9:17
references.pmid: 19405953
references.citation: Nature. 2011 May 25;474(7351):380-4
references.pmid: 21614001
references.citation: Nat Rev Genet. 2008 Jun;9(6):465-76
references.pmid: 18463664
references.citation: Addict Biol. 2014 Jan;19(1):102-10
references.pmid: 21995595
references.citation: Neuropsychobiology. 2009;60(1):49-54
references.pmid: 19729973
references.citation: J Clin Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57
references.pmid: 9881538
references.citation: Am J Med Genet A. 2004 Nov 15;131(1):11-7
references.pmid: 15386471
references.citation: Am J Hum Genet. 2008 Mar;82(3):696-711
references.pmid: 18319075
references.citation: JAMA. 2007 Mar 7;297(9):940
references.pmid: 17341698
references.citation: Hum Mol Genet. 2012 Jan 15;21(2):371-83
references.pmid: 21994764
references.citation: Mol Psychiatry. 2011 Dec;16(12):1213-20
references.pmid: 20877284
references.citation: FASEB J. 2010 Aug;24(8):3036-51
references.pmid: 20375269
references.citation: Autism Res. 2008 Jun;1(3):169-78
references.pmid: 19132145
references.citation: Genome Res. 2009 Nov;19(11):1974-82
references.pmid: 19652013
references.citation: J Psychiatr Res. 2010 Oct;44(14):989-91
references.pmid: 20381070
references.citation: PLoS One. 2011 Jan 24;6(1):e16506
references.pmid: 21297937
references.citation: Dialogues Clin Neurosci. 2010;12(1):25-35
references.pmid: 20373664
references.citation: Hum Mol Genet. 2006 Oct 15;15 Spec No 2:R138-50
references.pmid: 16987877
references.citation: Nat Rev Genet. 2008 May;9(5):341-55
references.pmid: 18414403
references.citation: BMB Rep. 2008 Sep 30;41(9):615-25
references.pmid: 18823584
references.citation: J Mol Neurosci. 2011 Mar;43(3):443-52
references.pmid: 20957522
references.citation: Trends Genet. 1997 Aug;13(8):293-5
references.pmid: 9260513
references.citation: Epigenetics. 2006 Oct-Dec;1(4):e1-11
references.pmid: 17486179
references.citation: Transl Psychiatry. 2012 Mar 13;2:e91
references.pmid: 22832856
references.citation: PLoS One. 2012;7(12):e52570
references.pmid: 23285094
references.citation: Mol Psychiatry. 2007 Mar;12(3):292-306
references.pmid: 17189958