title: RET and PHOX2B genetic polymorphisms and Hirschsprung's disease susceptibility: a meta-analysis.
abstract: BACKGROUND
  Many publications have evaluated the correlation between RET, PHOX2B polymorphisms and Hirschsprung's disease with conflicting results. We performed this meta-analysis to clarify the association of RET, PHOX2B polymorphisms with HSCR.
  
  
  METHODS
  We searched Pubmed, Elsevier Science Direct, China National Knowledge Infrastructure database, Chinese Biomedical database, Google scholar. The combined odds ratio (OR) with 95% CI was calculated to estimate the strength of the association. Heterogeneity and publication bias were also assessed.
  
  
  RESULTS
  In total, 16 studies concerning RET and 4 studies concerning PHOX2B were included in the meta-analysis. The effects of five polymorphisms of RET (rs1800858, rs1800860, rs1800861, rs10900297, rs2435357) and one polymorphism (rs28647582) of PHOX2B were evaluated. We found a significant correlation between RET polymorphisms and HSCR. For rs1800858, the overall ORs (95% CI) of the A versus G, AA versus GG, AA/AG versus GG and AA versus GG/AG were 3.81 (2.28-6.35); 8.36 (3.45-20.25); 3.59 (1.83-7.02); and 6.60 (3.66-11.89). For rs1800861, the comparison of subjects in the G versus T, GG versus TT, GG/TG versus TT and GG versus TT/TG were 2.85(1.81-4.47); 5.38(2.68-10.80); 3.07(2.17-4.34) and 4.14(1.84-9.30) respectively. For rs10900297, the comparison results showed statistically significant. (OR(C versus A) = 5.05,95%CI = 4.16-6.13; OR(CC versus AA) = 9.73, 95%CI = 5.94-15.94; OR(CC/AC versus AA) = 5.31, 95%CI = 3.27-6.82; OR(CC versus AC/AA) = 7.06,95%CI = 5.60-8.91.) But, for rs1800860, the GG/GA versus AA did not reach statistical association (OR = 3.77, 95% CI = 0.94-15.07) and the G versus A, GG versus AA, GG versus GA/AA were 2.23 (1.60-3.11);4.56 (1.14-18.27); 2.38 (1.66-3.43) respectively. For rs2435357, the T versus C, TT versus CC, TT/TC versus CC and TT versus CC/TC were 4.53 (3.27-6.27); 11.44 (5.67-23.10); 4.04 (2.92-5.57), and 9.01(5.25-15.46).The single polymorphism of PHOX2B gene wasn't related to the risk for HSCR.
  
  
  CONCLUSIONS
  This meta-analysis shows a significant association between RET polymorphisms and HSCR.
authors.affiliation: Department of Hygiene Analysis and Detection, School of Public Health, Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Chun-mei
authors.initials: CM
authors.lastname: Liang
authors.affiliation: Department of Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Dong-mei
authors.initials: DM
authors.lastname: Ji
authors.affiliation: Department of Stomatology, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Hygiene Analysis and Detection, School of Public Health, Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Ling-ling
authors.initials: LL
authors.lastname: Ren
authors.affiliation: Department of Hygiene Analysis and Detection, School of Public Health, Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Hygiene Analysis and Detection, School of Public Health, Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Hai-yan
authors.initials: HY
authors.lastname: Zhang
mesh_terms: D020022:Genetic Predisposition to Disease; D006627:Hirschsprung Disease / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D017594:Publication Bias; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C109220:NBPhox protein; D014157:Transcription Factors; D051096:Proto-Oncogene Proteins c-ret