title: Identification of differentially methylated genes in normal prostate tissues from African American and Caucasian men.
abstract: OBJECTIVE
  Aberrant DNA methylation changes are common somatic alterations in prostate carcinogenesis. We examined the methylation status of six genes in prostate tissue specimens from African American (AA) and Caucasian (Cau) males.
  
  
  METHODS
  We used pyrosequencing to quantitatively measure the methylation status of GSTP1, AR, RARbeta2, SPARC, TIMP3, and NKX2-5. Real-time PCR was used to determine gene expression, and gene reactivation was analyzed by 5-aza-2'-deoxycytidine and/or trichostatin A treatment.
  
  
  RESULTS
  Statistical analysis showed significantly higher methylation in the prostate cancer tissue samples in comparison with matched normal samples for GSTP1 (P = 0.0001 for AA; P = 0.0008 for Cau), RARbeta2 (P < 0.001 for AA and Cau), SPARC (P < 0.0001 for AA and Cau), TIMP3 (P < 0.0001 for AA and Cau), and NKX2-5 (P < 0.0001 for AA; P = 0.003 for Cau). Overall, we observed significant differences (P < 0.05) in the methylation level for all genes, except GSTP1, in the AA samples in comparison with the Cau samples. Furthermore, regression analysis revealed significantly higher methylation for NKX2-5 (P = 0.008) and TIMP3 (P = 0.039) in normal prostate tissue samples from AA in comparison with Cau, and a statistically significant association of methylation with age for NKX2-5 (P = 0.03) after adjusting for race.
  
  
  CONCLUSIONS
  Our findings show higher methylation of several genes in prostate tissue samples from AA in comparison with Cau and may potentially contribute to the racial differences that are observed in prostate cancer pathogenesis.
authors.affiliation: Department of Medicine, Cancer Center, Howard University College of Medicine, Washington, District of Columbia 20060, USA. bkwabiaddo@howard.edu
authors.forename: Bernard
authors.initials: B
authors.lastname: Kwabi-Addo
authors.forename: Songping
authors.initials: S
authors.lastname: Wang
authors.forename: Woonbok
authors.initials: W
authors.lastname: Chung
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Jelinek
authors.forename: Steven R
authors.initials: SR
authors.lastname: Patierno
authors.forename: Bi-Dar
authors.initials: BD
authors.lastname: Wang
authors.forename: Ramez
authors.initials: R
authors.lastname: Andrawis
authors.forename: Norman H
authors.initials: NH
authors.lastname: Lee
authors.forename: Victor
authors.initials: V
authors.lastname: Apprey
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Issa
authors.forename: Michael
authors.initials: M
authors.lastname: Ittmann
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000368:Aged; D045744:Cell Line, Tumor; D019175:DNA Methylation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005796:Genes; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006262:Health; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015676:Osteonectin / Q000235:genetics; D011467:Prostate / Q000166:cytology / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D015676:Osteonectin; D011944:Receptors, Androgen; D018168:Receptors, Retinoic Acid; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D014157:Transcription Factors; C540966:retinoic acid receptor, beta2, human; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi