中文摘要：

目的通过对SIM2基因SNPs基因型与先天性巨结肠症（Hirschsprung disease，HsCR）的关联分析，探索可能潜在的致病基因，从遗传学上丰富HsCR临床表型的内容。方法采集107例临床确诊的HSCR患儿（病例组）和107例正常对照（对照组）的外周静脉血，提取白细胞基因组DNA，PCR扩增SIM2基因2个位点（rs2073416和rs2073601），将PCR产物测序进行突变筛选，明确突变位点和类型，并进一步结合病例一对照和生物信息学分析探讨变异的功能意义。结果病例组与对照组SIM2rs2073601AA和AC基因型频率无显著性差异（P〉0．05）；而病例组与对照组SIM2rs2073416AA、AG和GG基因型频率及A和G等位基因频率差异显著（P〈0．05），AA和GG基因型及G等位基因的患病风险分别为0．021，0．080和0．002。SIM2基因rs2073416测序共检出2种单碱基的替换，第437位密码子核苷酸C盯。CAG突变和第437位密码子核苷酸ar]r—AAG突变。结论中国HSCR人群存在着SIM2基因突变，具有一定的遗传性。

英文摘要：

Objective To identify the correlation of SIM2 SNPs genotypes to the clinical phenotypes of Hirschsprung＇s disease （HSCR）. Methods Genomic DNA of peripheral blood leukocytes was abstracted from 107 cases with HSCR and 107 normal control children. PCR amplification of SIM2 gene （rs2073416 and rs2073601）, PCR products were sequenced for mutation screening. Case-control study and bioinformatic analysis were utilized to explore the potential functional roles of the variations detected. Results No significant differences were found in SIM2 gene rs2073601 allele and genotype frequencies of CC and CT between patients with HSCR and the control group （P 〉 0. 05）. The allele and genotype frequencies in SIM2 gene rs2073416 as well as the genotypes of AA, AG and GG were found to be significantly different between patient and control groups （P〉0. 05）. A/G polymorphism was detected in HSCR patients. The genotypic of AA and GG and the allelic gene of G with diseases risk were 0. 021, 0. 080 and 0. 002 respectively. Two kinds of single nucleotide substitution were detected in the HSCR patients in the SIM2 gene rs2073416 situ. Heterozygosity for rs2073416 were confirmed in the HSCR： CTT-CAG mutation and CTT-AAG at position 437. Conclusions The results suggest that the mutation of the SIM2 gene may have a high frequency in Northern China patients with HSCR, and HSCR has the heredity tendency.