RET and PHOX2B genetic polymorphisms and Hirschsprung's disease susceptibility: a meta-analysis

Chun-mei Liang; Dong-mei Ji; Xu Yuan; Ling-ling Ren; Juan Shen; Hai-yan Zhang

doi:10.1371/journal.pone.0090091

RET and PHOX2B genetic polymorphisms and Hirschsprung's disease susceptibility: a meta-analysis

PLoS One. 2014 Mar 20;9(3):e90091. doi: 10.1371/journal.pone.0090091. eCollection 2014.

Authors

Chun-mei Liang¹, Dong-mei Ji², Xu Yuan³, Ling-ling Ren¹, Juan Shen¹, Hai-yan Zhang¹

Affiliations

¹ Department of Hygiene Analysis and Detection, School of Public Health, Anhui Medical University, Hefei, People's Republic of China.
² Department of Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
³ Department of Stomatology, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.

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.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Genetic Predisposition to Disease*
Hirschsprung Disease / genetics*
Homeodomain Proteins / genetics*
Humans
Polymorphism, Single Nucleotide / genetics*
Proto-Oncogene Proteins c-ret / genetics*
Publication Bias
Transcription Factors / genetics*

Substances

Homeodomain Proteins
NBPhox protein
Transcription Factors
Proto-Oncogene Proteins c-ret

Grants and funding

This was funded by the Youth Foundation Training Programme of National Natural Science Foundation of the First Affiliated Hospital of Anhui Medical University (No. 2010KJ24). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.