汉族儿童TPMT基因全蛋白编码区SNP检测与分析

Detection and analysis for single nucleotide polymorphism of protein-coding region of TPMT gene in Chinese Han children

目的分析汉族儿童巯嘌呤甲基转移酶(TPMT)基因的蛋白质编码区(CDS)突变,探讨其在急性白血病(AL)患儿中的单核苷酸多态性(SNP)。方法变性梯度凝胶电泳结合DNA测序检测103例AL患儿及111例对照组儿童的TPMT基因CDS碱基位点突变情况。结果汉族儿童TPMT基因筛查出2个蛋白编码区单核苷酸多态性(cSNPs),分别为TPMT*3C(A719G)和*1S(C474T)。TPMT*3C AA、AG、GG基因型频率在AL患儿组中分别为95.1%、3.9%和1.0%,在对照组中分别为97.3%、2.7%和0,其G等位基因频率分别为2.9%和1.4%;TPMT*1S CC、CT、TT基因型频率在AL患儿组分别为5.8%、24.3%和69.9%,在对照组中分别为8.1%、28.8%和63.1%,其C等位基因频率分别为18.0%和22.5%。2个cSNPs基因型及等位基因频率在两组中分布差异无统计学意义(P>0.05)。对照组筛查出C210T和TPMT*26(T622C)基因突变。结论汉族儿童存在TPMT*26突变基因型,且TPMT*3C、TPMT*1S可能均与儿童AL易感性无关。

Objective To analyze the mutations of the coding DNA sequence （CDS） of thiopurine methyltransferase （TPMT） gene in Chinese HaM children, and explore their distribution of single nucleotide polymorphism （SNP） in the children with acute leukemia （AL）. Methods The mutations of base loci in CDS of TPMT of 103 children with AL and 111 controls were detected by denaturing gradient gel electrophoresis （DGGE） combining with DNA sequencing. Results Only two coding-region single nucleotide polymor- phisms （cSNP） in the CDS of TPMT gene, ^＊ 3C and ^＊1 S, were found by the screening the Chinese Han children. Genotypic frequen-cies of AA, AG and GG of TPMT^＊ 3C were 95.1%, 3.9%, 1.0% and 97.3%, 2.7%, 0, and the allele frequencies of G were 2.9% and 1.4% in the patients and controls respectively. Genotypic frequencies of CC, CT and TT of TPMT^＊ 1S were 5.8%, 24.3%, 69.9% and 8.1% , 28.8% , 63.1%, and the allele frequencies of C were 18.0% and 22.5% in the patients and controls respectively. There were no significant differences for the distribution of cSNPs between the two groups （P 〉 0. 05）. Two mutations, C210T and T622C, reported previously were detectable in controls. Conclusion TPMT^＊ 26 was found in HaM children. There may be no correlations between TPMT^＊ 3C or ^＊ 1S and the risk of AL in the children.