DNMT3B基因启动子单核苷酸多态性C46359T与急性白血病的关系

目的探讨DNMT3B基因启动子C46359T单核苷酸多态性与急性白血病(AL)发病的关系。方法采用PCR-RFLP结合DNA测序技术检测160例AL患者及240例正常对照DNMT3B基因启动子C46359T单核苷酸多态性。结果中国汉族人中CT杂合型的频率为2·5%,TT纯合型的频率为97·5%,未检出CC纯合型;与美国白种人的基因型分布(三种基因型频率分别为41·8%、23·2%和35·0%)存在显著差异(P<0·001)。在160例初发的成人AL患者中CT杂合型的频率为10·6%,明显高于正常对照组(2·5%),P<0·001,提示在AL患者中CT基因型是一个高发现象。正常人中CT基因型发生AL的危险性是TT基因型的4·669倍(OR=4·669,95%可信区间为1·700~14·747),说明CT基因型与AL的发生有一定的相关性。结论DNMT3B基因启动子-149位CT基因型与AL发病相关;中国汉族人的DNMT3B基因启动子-149位基因型分布与美国白种人有显著不同。

The C46359T polymorphism of DNMT3B promoter gene and pathogenesis of acute leukemia

Objective To explore the relationship between the polymorphism of C46359T in DNMT3B promoter and the pathogenesis of acute leukemia(AL). Methods PCR-RFLP and DNA sequencing were used to analyze the genotypic polymorphism C46359T of promoter in genomic DNA of bone marrow cells / blood lymphocytes from 160 patients with AL and 240 normal controls. Results In people of the Hans in China, genotypic frequencies of 2.5% ( CT ), 97.5%( TT ) and 0(CC) were statistically significant ((P<0.001)) comparing with the genotype frequencies of 41.8% (CT), 23.2% (TT) and 35.0% (CC) in Caucasian in USA. The genotypic frequency of CT heterozygote in 160 AL patients was 10.6%, significantly higher than that in the control subjects (2.5%, P<0.001), indicating that the CT heterozygote might be a more frequent phenomenon in AL. Compared with TT homozygote, CT heterozygote had a 4.669-fold increased risk of acute leukemia (OR=4.669; 95% confidence interval 1.700-14.747). It was suggested that CT heterozygote was relative to the pathogenesis of AL. Conclusions Different distribution of genotypes in different races, the CT heterozygote was relative to the pathogenesis of AL.