DNMT3B基因启动子单核苷酸多态性C46359T与急性白血病的关系

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

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.

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 4l. 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 Tr 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.