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目的观察中国汉族散发性先天性巨结肠症(sHD)G蛋白藕联受体家族的内皮素受体-B(EDNRB)易感基因的突变与多态性特征,探讨碱基改变与先天性巨结肠症的发病关系。方法收集104例散发性先天性巨结肠与其中42例患儿(子代组)的双亲血样,120例正常儿童作对照,聚合酶链反应-单链构象多态性(PCR-SSCP)与DNA测序确定并比较EDNRB基因外显子1、2的突变与多态性位点(SNPs)等位基因与基因型分布差异,分析sHD表型与SNPs的关联,传递不平衡检验(TDT)分析三样本家系SNPs的传递不平衡。结果EDNRB基因外显子1、2均未发现突变,外显子1检测2个S NPs,c311 A→T(N104I)为新发现位点;病例组c311 A→T位点的等位基因和基因型频率均与对照组差异有统计学意义(P<0.01),c99C→T位点的差异无统计学意义;TDT检验发现亲子代间在c311 A→T(N104I)位点存在传递不平衡,杂合体双亲优先传递等位基因T给子代;临床表型与SNPs等位基因分布无明显关联。结论中国汉族散发性先天性巨结肠EDNRB基因的多态性可能在发病中起重要作用。
Objective To investigate the mutations and polymorphisms of endothelin receptor-B (EDNRB) susceptibility gene in sporadic GHD patients in Chinese Han population. To investigate the relationship between the changes of nucleotide and congenital giant The incidence of colonic disease. Methods The blood samples of 104 sporadic Hirschsprung’s disease patients and 42 children (offspring) were collected and compared with 120 normal children. PCR-SSCP and DNA Sequencing was performed to identify and compare the distribution of alleles and genotypes between mutations and polymorphisms (SNPs) in exon 1 and exon 2 of EDNRB gene. The association between sHD phenotypes and SNPs was analyzed. Transmission disequilibrium test (TDT) Sample family SNPs are not evenly distributed. Results There were no mutations in exon 1 and exon 2 of EDNRB gene. Two SNPs were detected in exon 1 and c311 A → T (N104I) was found as a new locus. The allele of c311 A → T locus (P <0.01). The difference of c99C → T loci was not statistically significant. The TDT test showed that there was an imbalance in transmission between c311 A → T (N104I) loci , Parents of hybrids preferentially transmitted alleles T to offspring. There was no significant correlation between clinical phenotypes and alleles of SNPs. Conclusion The polymorphism of EDNRB gene in Chinese Han sporadic Hirschsprung may play an important role in the pathogenesis.