Association of LRP5/6 gene polymorphism and Hirschsprung's disease

Abstract

Objective To explore the relationship between low density lipoprotein receptorre lated protein 5/6 (LRPS/6) genes and the genotypes of single nucleotide polymorphisms (SNPs) of Hirschsprung's disease (HD).Methods A total of 200 children of HD (case group) and 200 healthy children (control group) were recruited to obtain genomic DNA from peripheral blood leukocytes.Pol ymerase chain reaction (PCR) amplification was performed for LRPS/6 genes (rs121908674,rs121908671/rs121918313,rs117554756) and PCR products were sequenced for mutation screening.Cas-control study and bioinformatic analyses were utilized to explore the potential roles of variations.Results No significant inter group differences existed in allelic and genotypic frequencies of AA and AG for rs121908671 (P＞0.05).LRP6 gene rs117554756 allelic and genotypic frequencies of AA and AC existed between patients with HD and the control group (P＞0.05).The allelic and genotypic fre quencies in LRP5 gene rs121908674 as well as the genotypes of CC,CG and GG were related in two groups (P＜0.05).C and G polymorphisms were present in HD.The disease risks of genotype of CC and GG and allelic gene of G were 0.005,0.195 and 0.001 respectively.The allelic and genotypic fre quencies in LRP6 gene rs121918313 and the genotypes of CC,CT and TT were related in two groups (P＜0.05).C and T polymorphisms were present in HD.The disease risks of genotype of CC and CT and allelic gene of T were 0.012,0.504 and 0.003 respectively.And rs121918313 sequencing demon strated a loss of heterozygosity and single nucleotide substitution.The single nucleotide substitution for rs121918313 was confirmed in HD:AAA→CAA at position 131.Conclusions The polymor phisms may affect HD in LRP5/6 genes so as to carry a hereditary tendency. Key words: Hirschsprung disease; Polymorphism; Genotype