RET基因启动子区遗传变异与先天性巨结肠合并小肠结肠炎风险  

Correlations between polymorphisms in RET promoter and risk of Hirschsprung′s disease associated enterocolitis

作　　者：王斌[1] 刘磊[1] 毛健雄[1] 陈芳[1] 

机构地区：[1]深圳市儿童医院,广东518026

出　　处：《中国优生与遗传杂志》2008年第2期24-25,共2页Chinese Journal of Birth Health & Heredity

摘　　要：目的先天性巨结肠(Hirschsprung′s disease,HSCR)是一种肠神经系统发育异常导致的先天性消化道畸形,巨结肠合并小肠结肠炎是最常见的严重并发症之一。RET基因是HSCR的主要致病基因,本研究探讨RET启动子区的两个功能性单核苷酸多态-5G/A和-1A/C与先天性巨结肠合并小肠结肠炎风险的关系。方法以聚合酶链反应(PCR)和直接测序(direct-squencing)分析方法,检测了52例先天性巨结肠患者,其中合并小肠结肠炎者18例和120例正常对照者RET-5G/A和-1A/C的基因型,比较不同基因型与疾病风险的相关性。结果RET-5AA和-1CC基因型频率在先天性巨结肠患者和正常对照中的分布有显著性差异,其中以-5AA较显著(P值<0.001)。此外,与正常对照组相比,携带RET-5AA基因型者罹患先天性巨结肠合并小肠结肠炎的风险亦增加(P值=0.004),但与单纯HSCR患者组相比,RET-5AA基因型者并无增加合并小肠结肠炎的风险(P值=0.461)。结论RET基因启动子区遗传变异-5G/A和-1A/C与先天性巨结肠合并小肠结肠炎风险增加相关,但并不增加原有HSCR患者合并小肠结肠炎的风险。Objective： Hirschspmng＇s disease associated enterocolitis （HAEC） is a severe complication of HSCR, which is a congenital disorder characterized by an absence of ganglion cells in the nerve plexuses of the lower digestive tract. The major HSCR gene is RET, in which the promoter variations, -5G/A and - 1A/C, were identified to be functional. This case -control study examined the contribution of these variations to susceptibility of HAEC. Methods： Genotypes were determined in 52 patients with HSCR, including 18 HAEC and 120 norreal controls. The χ2 and Fish exact test were used to calculate statistical difference. Results： We found a significantly increased risk of HSCR associated with homozygous genotypes of the RET-5AA or RET- 1CC compared with the RET-5GG or RET- 1AA （ P value 〈 0.001） genotypes, respectively. Furthermore, RET-5GG was identified to be associated with increased risk of HAEC when compared with normal controls, but not associated when compared with HSCR only （ Pvalue = 0. 461）. Conclusion： These findings suggest that RET variations -5G/A and -1A/C may not increase the risk of HAEC among HSCR patients.

关 键 词：巨结肠合并小肠结肠炎 RET 基因遗传变异 分子遗传学 

分 类 号：R726.5[医药卫生—儿科]