GGH基因多态性研究及一个新的错义突变T191G的发现

A Novel Missense Mutation(T191G) Identified in y-glutamyl Hydrolase Gene

目的:研究γ-谷氨酰水解酶基因(γ-glutamyl hydrolase,GGH)T16C单核苷酸多态性(single nucleotide polymorphism,SNP)在急性白血病(acute leukemia,AL)患儿和正常儿童中的频率分布特征,并以期发现新的多态性位点。方法:应用DNA直接测序技术,对90例AL患儿和120例正常儿童的cDNAs进行GGH T16C基因型的筛查。结果:在GGH的第2外显子发现一新的错义突变T191G,导致第64位氨基酸由亮氨酸(Leu)被色氨酸(Trp)替代。首次鉴定了中国儿童GGH T16C多态性,其在AL患儿及正常儿童中的等位基因频率分别为20.0%和17.1%,两组间的等位基因频率差异无统计学意义(P>0.05),表明与白血病的易感性无相关性。结论:首次确定了国内汉族儿童GGH T16C的等位基因频率,并发现一新的错义突变GGHT191G。

Objective： This study aims to investigate the distribution ofy-glutamyl hydrolase gene （ GGH ） T16C genotype and allele frequency in children with acute leukemia （ AL ） and healthy children and to identify the novel single nucleotide polymorphism （ SNP ）. Methods： Bone marrow samples from 90 children with AL and peripheral blood samples from 120 healthy children （ controls ） were obtained to prepare complementary DNA （ eDNA ）. The eDNA was analyzed for the polymorphism in GGH T16C by direct sequencing. Results： A novel missense mutation was a T--＋G transition in the second nucleotide of codon 64 in exon 2 of the GGH gene, which was predicted to result in the substitution of leucine with tryptophan （ Leu 64 Trp ）. The T 16C polymorphism in the coding region of the GGH gene was first identified in Chinese children. The T 16C allelic frequency in the AL children was 20 %, whereas that in the control group was 17.1%. The allelic frequency of SNP was not associated with susceptibility to AL. Conclusion： This work is the first report concerning the examination ofT16C polymorphism of GGH in Chinese Han children. A novel GGH gene missense mutation T191G was identified in healthy Chinese children.