Association between IKBKAP polymorphisms and Hirschsprung's disease susceptibility in Chinese children.
Association between IKBKAP polymorphisms and Hirschsprung's disease susceptibility in Chinese children.
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DOI：
10.21037/tp-21-550
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发表时间：
2022-06
影响因子：
2
通讯作者：
中科院分区：
文献类型：
--
作者：
先天性巨结肠症(HSCR)是一种罕见的先天性疾病，其肠道远端神经系统(ENS)缺失。HSCR是一种涉及遗传因素和环境因素的疾病。尽管已经发现了一系列与HSCR相关的基因，但仍有许多与HSCR相关的基因尚未被发现。以往的研究已证实，HSCR的一个潜在易感基因是B细胞中Kappa轻多肽基因增强子的抑制因子--激酶复合体相关蛋白(IKBKAP)。本研究旨在探讨IKBKAP基因变异与中国南方儿童HSCR易感性的关系。采用MASS ARRAY IPLEX Gold System(Sequenom，San Diego，CA，USA)对1,470例HSCR患儿(病例组)和1,473例健康儿童(对照组)进行单核苷酸多态性(SNPs)基因分型。通过比较相应病例和对照样本中SNPs的等位基因频率，评估SNPs与HSCR或临床亚型的相关性。利用Plink 1.9软件对不同的遗传模型进行检验，包括加性模型、隐性模型和显性模型。进一步的亚群分析显示rs2275630为全结肠无神经节细胞增多症(TCA)特异性易感基因。本研究首次表明IKBKAP rs2275630与HSCR易感性有关，尤其是在TCA患者中。提示IKBKAP rs2275630是HSCR的易感基因。
Hirschsprung’s disease (HSCR) is a rare congenital disease in which enteric nervous system (ENS) in the distal intestine is absent. HSCR is a disease involving genetic factors and environmental factors. Despite a series of genes have been revealed to contribute to HSCR, many HSCR associated genes were yet not identified. Previous studies had identified that a potential susceptibility gene of HSCR was an inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex-associated protein (IKBKAP). The study aimed to explore the association of genetic variants in IKBKAP and HSCR susceptibility in southern Chinese children. Single nucleotide polymorphism (SNPs) were genotyped by the Mass ARRAY iPLEX Gold system (Sequenom, San Diego, CA, USA) on all samples, which included 1,470 HSCR children (cases) and 1,473 healthy children (controls). The associations between SNPs and HSCR or clinical subtypes were assessed by comparing their allele frequencies in corresponding case and control samples. Different genetic models, including additive, recessive, and dominant models, were tested using PLINK 1.9 software. Further subgroup analysis revealed rs2275630 as a total colonic aganglionosis (TCA)-specific susceptibility locus. The present study is the first to indicate that IKBKAP rs2275630 were associated with HSCR susceptibility, especially in TCA patients. We conclude that IKBKAP rs2275630 is a susceptibility gene of HSCR.
影响因子：
5.3
作者：
Tang CS;Sribudiani Y;Miao XP;de Vries AR;Burzynski G;So MT;Leon YY;Yip BH;Osinga J;Hui KJ;Verheij JB;Cherny SS;Tam PK;Sham PC;Hofstra RM;Garcia-Barceló MM
通讯作者：
Garcia-Barceló MM