Bahreini Fatemeh, Mahdavinezhad Ali, Eghbali Maryam
Department of Medical Genetics, Hamadan University of Medical Sciences, Hamadan, Iran.
Research Center for Molecular Medicine, Institute of Cancer, Hamadan University of Medical Sciences, Hamadan, Iran.
Iran J Public Health. 2025 Mar;54(3):567-577. doi: 10.18502/ijph.v54i3.18249.
Hirschsprung disease (HSCR) is a congenital life-threatening intestinal disorder characterized by the absence of nerves in the myenteric and submucosal plexuses in the distal bowel. There are several studies on the association of rs2435357 polymorphism in the proto-oncogene gene and HSCR susceptibility. However, some of the results remain controversial. Therefore, we conducted this updated meta-analysis to estimate the association of this polymorphism and HSCR risk.
We searched PubMed, Scopus, Web of Science and Google Scholar according to PRISMA guidelines to assess the association of rs2435357 with HSCR up to Jan 2024. We included case-control/cohort studies to perform meta-analysis conducted using genotype models. Odd ratios (ORs) with 95%CI were utilized to determine the susceptibility to HSCR. Q-test and I were used to evaluate heterogeneity, and Egger's/ Begg's tests were used to assess publication bias.
Overall, 89 eligible studies meeting the inclusion criteria were retrieved with 2690 cases and 5408 controls from online databases. Finally, 17 studies were used for meta-analysis. rs2435357 showed a statistically significant association with HSCR under allelic model (OR = 4.50, 95%CI: 3.78-5.36, <0.05), additive model (OR=2.02, 95%CI: 1.54-2.63, <0.05), recessive model (OR=4.39, 95%CI: 3.33-5.78, <0.05) and dominant model (OR=8.66, 95%CI: 6.96-10.76, <0.05).
The polymorphism rs2435357 in gene provides substantial susceptibility in all inheritance models and to HSCR. However, more research is needed to clarify its specific role in prognosis and the interaction with other genetic and environmental factors affecting HSCR.
先天性巨结肠症（HSCR）是一种危及生命的先天性肠道疾病，其特征是远端肠道的肌间神经丛和黏膜下神经丛中缺乏神经。关于原癌基因中rs2435357多态性与HSCR易感性的关联已有多项研究。然而，部分结果仍存在争议。因此，我们进行了这项更新的荟萃分析，以评估这种多态性与HSCR风险的关联。
我们根据PRISMA指南检索了PubMed、Scopus、Web of Science和谷歌学术，以评估截至2024年1月rs2435357与HSCR的关联。我们纳入病例对照/队列研究，使用基因型模型进行荟萃分析。采用95%置信区间的比值比（OR）来确定HSCR的易感性。Q检验和I²用于评估异质性，Egger检验/Begg检验用于评估发表偏倚。
总体而言，从在线数据库中检索到89项符合纳入标准的合格研究，包括2690例病例和5408例对照。最后，17项研究用于荟萃分析。在等位基因模型（OR = 4.50，95%CI：3.78 - 5.36，P < 0.05）、加性模型（OR = 2.02，95%CI：1.54 - 2.63，P < 0.05）、隐性模型（OR = 4.39，95%CI：3.33 - 5.78，P < 0.05）和显性模型（OR = 8.66，95%CI：6.96 - 10.76，P < 0.05）下，rs2435357与HSCR显示出统计学上显著的关联。
原癌基因中的多态性rs2435357在所有遗传模型中均对HSCR具有显著易感性。然而，需要更多研究来阐明其在预后中的具体作用以及与影响HSCR的其他遗传和环境因素的相互作用。
