Relationship between polymorphisms and haplotypes of RET gene and Hirschsprung's disease / 中华消化外科杂志

ABSTRACT

Objective To study the relationship between polymorphisms of RET gene and the incidence of Hirschsprung's disease, investigate the haplotypes of RET gene in patients with Hirschsprung's disease, and analyze the characteristics of single nucleotide polymorphisms of RET gene in Zhejiang Han population. Methods Peripheral blood samples were collected from 123 patients with Hirschsprung's disease and 194 healthy children from 2005 to 2007 at Children's Hospital of Zhejiang University. G enomic DNA was extracted from the peripheral blood, and the genotypes were analyzed using polymerase chain reaction and direct sequencing. The frequencies of haplotypes were estimated using the PHASE software. The frequencies of RET alleles of the 194 healthy children were compared with those of other races. The correlation between RET gene and Hirschsprung's disease was analyzed using the chi-square test, and it was expressed in the form of odds ratio and 95% confidence interval.Results Increased risk of Hirschsprung's disease was observed in homozygous genotypes of the RET alleles -5AA, - 1CC, c135AA and c2307GG when compared with other genotypes ( x2 =57. 775, 20.469, 57. 040,38. 869, P ＜ 0. 05 ). Increased risk of Hirschsprung's disease was also observed in RET alleles -5A, - 1 C,c135A, c2307G when compared with other alleles ( x2 = 85.114, 53.117, 77. 005, 70. 161, P ＜0.05). There was no relationship between the frequencies of the alleles and the types of Hirschsprung's disease ( x2= 0.048,0.265, 0. 395, 0.027, P ＞ 0.05 ). The percentage of patients with haplotype ACAG was 75.2%, which was significantly higher than that of 38.7% in healthy children ( x2 = 62. 776, P ＜ 0.05 ). The frequencies of Hirschsprung's disease-associated alleles of RET - 5A, c135A and c2307G in Chinese were significantly higher than thosein the Caucasians or Yorubas (P＜0.05). Conclusions RET -5G＞A, -1A ＞C, c135G＞A and c2307T ＞ G are associated with Hirschsprung's disease and haplotype ACAG is the core one in Zhejiang Han population. There is no relationship between the frequency of allele and the types of Hirschsprung's disease. The frequencies of alleles of RET -5A, c135A and c2307G in Chinese are significantly higher than those in the Caucasians or Yorubas.