RET和PHOX2B基因多态性与先天性巨结肠症易感性：一项荟萃分析。
RET and PHOX2B genetic polymorphisms and Hirschsprung's disease susceptibility: a meta-analysis.
作者信息
Liang Chun-mei, Ji Dong-mei, Yuan Xu, Ren Ling-ling, Shen Juan, Zhang Hai-yan
机构信息
Department of Hygiene Analysis and Detection, School of Public Health, Anhui Medical University, Hefei, People's Republic of China.
Department of Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
出版信息
PLoS One. 2014 Mar 20;9(3):e90091. doi: 10.1371/journal.pone.0090091. eCollection 2014.
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.
背景
许多出版物评估了RET、PHOX2B基因多态性与先天性巨结肠病之间的相关性，但结果相互矛盾。我们进行了这项荟萃分析，以阐明RET、PHOX2B基因多态性与先天性巨结肠病（HSCR）之间的关联。
方法
我们检索了PubMed、爱思唯尔科学Direct、中国知网数据库、中国生物医学数据库、谷歌学术。计算合并比值比（OR）及95%置信区间（CI）以估计关联强度。还评估了异质性和发表偏倚。
结果
荟萃分析共纳入16项关于RET的研究和4项关于PHOX2B的研究。评估了RET的5个多态性（rs1800858、rs1800860、rs1800861、rs10900297、rs2435357）和PHOX2B的1个多态性（rs28647582）的影响。我们发现RET基因多态性与HSCR之间存在显著相关性。对于rs1800858，A与G、AA与GG、AA/AG与GG以及AA与GG/AG的总体OR（95%CI）分别为3.81（2.28 - 6.35）；8.36（3.45 - 20.25）；3.59（1.83 - 7.02）；以及6.60（3.66 - 11.89）。对于rs1800861，G与T、GG与TT、GG/TG与TT以及GG与TT/TG的比较结果分别为2.85（1.81 - 4.47）；5.38（2.68 - 10.80）；3.07（2.17 - 4.34）和4.14（1.84 - 9.30）。对于rs10900297，比较结果显示具有统计学意义。（OR（C与A） = 5.05，95%CI = 4.16 - 6.13；OR（CC与AA） = 9.73，95%CI = 5.94 - 15.94；OR（CC/AC与AA） = 5.31，95%CI = 3.27 - 6.82；OR（CC与AC/AA） = 7.06，95%CI = 5.60 - 8.91。）但是，对于rs1800860，GG/GA与AA未达到统计学关联（OR = 3.77，95%CI = 0.94 - 15.07），G与A、GG与AA、GG与GA/AA分别为2.23（1.60 - 3.11）；4.56（1.14 - 18.27）；2.38（1.66 - 3.43）。对于rs2435357，T与C、TT与CC、TT/TC与CC以及TT与CC/TC分别为4.53（3.27 - 6.27）；11.44（5.67 - 23.10）；4.04（2.92 - 5.57）和9.01（5.25 - 15.46）。PHOX2B基因的单核苷酸多态性与HSCR风险无关。
结论
这项荟萃分析表明RET基因多态性与HSCR之间存在显著关联。
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