title: Correlating of GSTM1, GSTT1, and GSTP1 genetic polymorphisms with the risk and expressions in children with isolated Hirschsprung disease.
abstract: OBJECTIVE
  The present study aimed to examine an association between the glutathione S-transferases (GSTs) polymorphisms (GSTM1, GSTT1, and GSTP1) genetic polymorphisms with the risk and expression in children with isolated Hirschsprung disease (HD).
  
  
  METHODS
  GSTM1, GSTT1, and GSTP1 genetic polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism analysis in 80 HD and 180 normal children (controls). The genic expressions were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The protein expressions were detected by Western blot.
  
  
  RESULTS
  The GSTM1 null genotype especially is associated with a greater risk of HD (X(2) = 1.129, P = 0.288, OR = 0.851, 95% CI = 0.632-1.146). The GSTT1 null genotype especially is associated with a greater risk of HD (X(2) = 6.165, P = 0.013, OR = 1.472, 95% CI = 1.084-1.999). The GSTP1 null genotype especially is associated with a greater risk of HD (X(2) = 4.748, P = 0.029, OR = 0.701, 95% CI = 0.509-0.964). GSTP1 and GSTP1 expressions were higher than GSTM1 in HD patients. Positive expressive rate of the GSTT1 and GSTP1 were 40.56% and 56.67% in HD. The mRNA and protein expressions level of GSTT1 and GSTP1 genes were significantly higher in HD than controls (P < 0.05). Positive expressive rate of the GSTM1 was 10.56% in HD. The GSTM1 was low expressed between in HD and controls (P > 0.05).
  
  
  CONCLUSIONS
  The GSTP1 genetic polymorphisms correlate to HD. We postulate that inherited gene deletion of GSTT1 and GSTP1 may produce increased genotoxic susceptibility for HD respectively, following exposure to xenobiotics that are substrates for these enzymes.
authors.affiliation: Laboratory of Pediatric Congenital Malformation, Ministry of Public Health, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China. gaohong515@vip.sina.com
authors.forename: Hong
authors.initials: H
authors.lastname: Gao
authors.forename: Rong
authors.initials: R
authors.lastname: He
authors.forename: Xiaojing
authors.initials: X
authors.lastname: He
authors.forename: Zhibo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Dajia
authors.initials: D
authors.lastname: Wang
authors.forename: Liangying
authors.initials: L
authors.lastname: Lv
authors.forename: Weilin
authors.initials: W
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000483:Alleles; D015153:Blotting, Western; D002648:Child; D004587:Electrophoresis, Agar Gel; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi / Q000235:genetics* / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006627:Hirschsprung Disease / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012015:Reference Standards; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D012333:RNA, Messenger; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human