RET基因多态性与中国湖北地区汉族人群先天性巨结肠的相关性研究  

Association between RET proto-oncogene polymorphisms and Hirschsprung disease in Chinese Han population of Hubei district

作　　者：杜寒松[1] 王国斌[1] 张颖[2] 陶凯雄[1] 汤绍涛[1] 牛彦锋[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院普通外科,武汉430022 [2]武汉大学中南医院基因诊断中心

出　　处：《中华胃肠外科杂志》2006年第2期152-156,共5页Chinese Journal of Gastrointestinal Surgery

基　　金：国家自然科学基金项目(30371397)

摘　　要：目的建立中国汉族人群RET基因位于exon2(密码子45)、exon13(密码子769)、exon11(密码子691)和exon15(密码子904)的基因多态性的基因型和等位基因频率的分布背景,探讨其基因多态性与先天性巨结肠的关系。方法应用PCR-RFLP在中国湖北地区汉族人群中检测正常对照组(122例)及散发性先天性巨结肠组(HD组,94例)G45A(GCG→GCA)、T769G(CTT→CTG)、G691A(GGT→AGT)和C904G(TCC→TCG)的单核苷酸多态性(singlenucleotidepolymorphisms,SNPs)。结果G45A、T769G和G691A在对照组中均存在多态性,但未发现C904G存在基因多态性,均为CC型。G45A在对照组中的基因型频率分别为AA0.17、AG0.72和GG0.11,突变型A和野生型G等位基因的频率为0.53和0.47;而G45A在HD组则分别为AA0.61、AG0.35和GG0.04,突变型A和野生型G等位基因的频率为0.78和0.22。T769G在对照组中基因型频率分布分别为GG0.30、GT0.52和TT0.18,G和T等位基因的频率为0.56和0.44;而T769G在HD组则分别为GG0.49、GT0.36和TT0.15,突变型G和野生型T等位基因的频率为0.67和0.33。两组间的两个位点的基因型和等位基因的分布频率差异均有统计学意义(χ2=28.64,P<0.001;χ2=5.27,P=0.022)。G691A在对照组中基因型频率分别为AA0.05、AG0.16和GG0.79,突变型A和野生型G等位基因的频率为0.13和0.87;而在HD组则分别为AA0.02、AG0.14和GG0.84,突变型A和野生型G等位基因的频率为0.09和0.91,两组间比较差异无统计学意义(χ2=1.232,P=0.267)。结论在中国湖北地区汉族人群中,RET密码子904可能不存在基因多态性,未发现G691A与先天性巨结肠存在相关性,而G45A和T769G的基因多态性可能与中国湖北地区汉族人群先天性巨结肠相关。Objective To establish the genetic background of exon2, exon13, exonl 1 and exon15 polymorphisms of RET proto-oncogene and study the possible involvement of RET proto-oncogene in the etiology of Hirschsprung disease （HD） in Chinese Han population surrounding Province HuBei. Methods The genotype and allele frequencies of RET proto-oncogene polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphisms （PCR-RFLPS） in 94 HD patients and 122 control subjects. Results The genotype and allele frequencies of exon2 were AA 0. 17, AG 0.72, GG 0. 11, A 0.53, G 0. 47 in control, and AA 0. 61, AG 0. 35, GG 0. 04, A 0. 78, G 0. 22 in HD, and those of exon13 were GG 0. 30,GT 0. 52,TT 0. 18,G 0. 56,T 0.44 in control, and GG 0. 49,GT 0. 36,TT 0. 15, G 0. 67,T 0.33 in HD. There were significant differences in the two polymorphisms above between HD and control. The genotype and allele frequencies of exon 11 were AA 0.05 ,AG 0. 16,GG 0.79 ,A 0. 13, G 0. 87 in control and AA 0. 02,AG 0. 14,GG 0. 84, A 0. 09, G 0.91 in HD,the differences were not found between these two groups about this site. Exon 15 were all of CC genotype in spite of control or HD. Conclusions These data provide evidences for the contributions of exon2 and exon 13 polymorphisms of RET proto-oncogene to susceptibility to HD in Chinese Han population surrounding province Hubei.

关 键 词：HIRSCHSPRUNG病 原癌基因 ret 基因多态性 

分 类 号：R726.5[医药卫生—儿科]