中文摘要：

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SNPs，c311A→T（N104I）为新发现位点；病例组c311A→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c311A→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。

英文摘要：

Objective To study the characteristics of mutations and polymorphisms of susceptibility gene EDNRB in Chinese patients of Han ethnicity with Hirschsprung disease （HD） and analyze the relationship between nucleotide change and HD. Methods Peripheral blood samples from 104 patients with sporadic HD,84 parents of 42 patients and 120 normal children as controls were collected. By using PCR-SSCP and direct DNA sequencing, mutations and polymorphisms of exon-1 and exon-2 in EDNRB gene were detected. The differences of allele frequencies and genotype distribution in polymorphic sites were further analyzed among three groups. Allele frequencies of SNPs in 42 slid trios were analyzed by transmission disequilibrium test （TDT） ,and the association between phenotype of HD and SNPs was ana- lyzed. Results No mutant sites were detected in exon-1 and exon-2 of EDNRB gene in patients with sliD. Two polymorphic sites were detected. Moreover c311 A→T（N104I） was a novel polymorphic site. The allele frequency and genotype frequency in c311 A→T were statistically different between case group and control group （ P 〈 0.01 ）, and no significant difference in c99C→T. TDT indicated a nonrandom association of transmitting specific alleles to patients,and the T allele （ c311 A → T） was preferentially transmitted to filial generation. No significant correlation was detected between phenotype and SNPs. Conclusion The polymorphisms of EDNRB in Chinese patients of Han ethnicity with sporadic HD may play an important role in the pathogenesis of HD.