Relationship between single nucleotide polymorphism in Smad-interacting protein-1 gene (rs41292293 and rs34961586) and Hirschsprung's disease

Abstract

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. Key words: Hirschsprung disease; Smad-interacting protein 1 gene; Polymorphism; single nu-cleotide; Alleles