CAJ | 학술논문

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(polyrnerase 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χ2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SIP1 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HSCR SNPs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SIP1 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HSCR SNPs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;rs34961586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.
목적 탐토SIP1기인단핵감산다태성(Single Nucleotide Polymorphisms,SNPs)rs41292293화rs34961586여선천성거결장병(Hirschsprung disease,HSCR)관계,위평고HSCR환병풍험전정기출.방법 제취병례조(HSCR환인)화대조조(정상건강인)각180예외주혈기인조DNA,취합매련반응(polyrnerase chain reaction,PCR)법확증SIP1기인2개외현자(exon5-rs41292293화exon6-rs34961586),PCR산물용한제성내절매HhaⅠ화RsaⅠ소화여측서,이진일보학정기인돌변위점,응용χ2검험통계분석병례조화대조조등위기인빈솔、기인형빈솔급기환병풍험.결과 HSCR조여대조조SIP1 rs41292293 GA화GG기인형빈솔급A화G등위기인빈솔차이현저(P<0.05),AA기인형고우GG기인형,AG재HSCR조중존재다태성,대조조여HSCR SNPs기인형분포GA、AA화GG분별위48.89%、35.00%화16.11%여37.78%、49.44%화12.78%,비교발현A(68.33%)화G(31.67%)등위기인빈솔유현저성차이(P<0.05);HSCR조여대조조SIP1 rs34961586 GC화GG기인형빈솔급C화G등위기인빈솔차이현저(P<0.05),GG기인형현저고우CC기인형,GC재HSCR조중존재다태성,대조조여HSCR SNPs기인형분포GC、GG화CC분별위34.44%、56.11%화9.45%여46.11%、39.44%화14.45%,비교발현G(65.83%)화C(34.17%)등위기인빈솔유현저성차이(P<0.05).측서rs41292293제268화256위밀마자핵감산CCC→CGA화TGG→TGT잡합돌변;rs34961586제135위밀마자핵감산CCA→CAC、TGC→TTC화TGC→TGG잡합돌변.결론 SIP1 rs41292293화rs34961586여HSCR적발생유밀절관계.위진일보연구해기인SNPs여기생리공능화질병적관계제공기출자료.
Objective To investigate the relationship between single nucleotide polymorphisms (SNPs) in Smad-interacting protein-1 (SIP1) (rs41292293 and rs34961586) and Hirschsprung's dis-ease (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-rs4961586 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 HI) 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 (GC, 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 mu-tation 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→ TGG 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 fur-ther study on the relationship between HD and SNPs in SIP1.