中文摘要：

目的探讨SIP1基因单核苷酸多态性（Single Nucleotide Polymorphisms，SNPs）rs41292293和rs34961586与先天性巨结肠病（Hirschsprung disease，HSCR）关系，为评估HSCR患病风险奠定基础。方法提取病例组（HSCR患儿）和对照组（正常健康人）各180例外周血基因组DNA，聚合酶链反应（polymerase chain reaction，PCR）法扩增SIP1基因2个外显子（exon5-rs41292293和exon6-rs34961586），PCR产物用限制性内切酶HhaI和RsaI消化与测序，以进一步确定基因突变位点，应用X^2检验统计分析病例组和对照组等位基因频率、基因型频率及其患病风险。结果HSCR组与对照组SJP1 rs41292293 GA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基因型高于GG基因型，AG在HSCR组中存在多态性，对照组与HSCRSNPs基因型分布GA、AA和GG分别为48．89％、35．00％和16．11％与37．78％、49．44％和12．78％，比较发现A（68．33％）和G（31．67％）等位基因频率有显著性差异（P〈0．05）；HSCR组与对照组SIPI rs34961586 GC和GG基因型频率及C和G等位基因频率差异显著（P〈0．05）,GG基因型显著高于CC基因型，GC在HSCR组中存在多态性，对照组与HSCRSNPs基因型分布GC、GG和CC分别为34．44％、56．11％和9．45％与46．11％、39．44％和14．45％，比较发现G（65．83％）和C（34．17％）等位基因频率有显著性差异（P〈0．05）。测序rs41292293第268和256位密码子核苷酸CCC→CGA和TGG→TGT杂合突变；rs3496i586第135位密码子核苷酸CCA—CAC、TGC→TTC和TGC—TGG杂合突变。结论SIP1 rs41292293和rs34961586与HSCR的发生有密切关系。为进一步研究该基因SNPs与其生理功能和疾病的关系提供基础资料。

英文摘要：

Objective To investigate the relationship between single nucleotide polymorphisms （SNPs） in Smad-interacting protein-1（SIP1） （rs41292293 and rs34961586） and Hirschsprung＇s disease （HD）. Methods The genotypes of SIP1 gene SNPs were detected in 180 patients with HD （HD group） and 180 healthy blood donors （control group）. DNA was extracted with standard methods. Polymerase chain reaction （PCR） was applied to detect exon5-rs41292293 and exon6-rs34961586 of SIP1. Subsequently, the PCR products were digested with restrictive endonuclease and sequenced by the direct sequencing method. The frequencies of allele and genotypes in both groups were analyzed with Chi-square test. Results Significant difference was noted in the frequencies of the allele （A, G） and genotypes （GA, GG） in SIP1 gene rs41292293 between the HD group and control group （P〈0. 05）. Polymorphism of AG was noted in patients with HD. The genotypic frequencies of GA, AA and GG in the control group and HD group were 48. 89% vs 37. 78%, 35.00% vs 49. 44%, and 16. 11% vs 12. 78%, respectively. Allele frequencies of A （68. 33%） and G （31.67%） were related with HD （P〈0. 05）. Frequencies of the allele （C, G） and genotypes （CC, GG） in SIP1 gene rs34961586 were related with HD. Polymorphism of CG was noted in the HD group. The genotypic frequencies of GC, GG and CC in the control group and the HD group were 34. 44% vs 46. 11%, 56. 11% vs 39. 44%, and 9. 45% vs 14. 45%, respectively. Allele frequency of G （65.83%） and C （34. 17%） was related to the HD （P 〈 0. 05）. Heterozygosity of rs41292293 was noted in the HD group as follows： CCC→CGA mutation at position 268 and TGG→TGT mutation at position 256.Heterozygosity of rs34961586 was also noted in the HD group： CCA→CAC, TGC→TTC and TGC→TGC- mutation at position 135. Conclusions SIP1 rs41292293 and rs34961586 allelic variation may be closely related to the pathogenesis of HD. This study provides some primary laboratory data for