Association between DNA methyltransferases 3B gene polymorphisms and the susceptibility to acute myeloid leukemia in Chinese Han population.
Association between DNA methyltransferases 3B gene polymorphisms and the susceptibility to acute myeloid leukemia in Chinese Han population.
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DNA甲基转移酶3B基因多态性与中国汉族人群急性髓系白血病易感性的关系
DOI：
10.1371/journal.pone.0074626
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Su J
中科院分区：
文献类型：
--
作者：
Zheng Q;Zeng TT;Chen J;Liu H;Zhang H;Su J
DNMT3B在癌变过程中异常甲基化的产生中起着至关重要的作用。DNMT3B基因的多态性可能影响DNMT3B的DNA甲基化酶活性，从而调节对AML的易感性。因此，我们研究了中国汉族人群中dnmt3b基因snp及其单倍型与AML风险之间的关系。采用HRM检测317例新发AML患者和406例年龄和性别匹配的健康对照者的DNMT3B基因型。在本研究调查的5个snp中，rs2424913在中国汉族人群中未发现多态性，rs1569686和rs2424908与AML风险显著相关。与TT基因型相比，rs1569686的GG基因型与AML风险增加相关（OR: 5.76; 95%CI: 2.60 ~ 12.73； P<0.01），与携带C等位基因的个体相比，携带G等位基因的个体患AML的风险显著增加（OR: 1.89; 95%CI: 1.41 ~ 2.52； P<0.01），这种多态性可以预测少数患者的AML风险。虽然与TT基因型相比，rs2424908的CC基因型似乎降低了AML的风险（OR: 0.57; 95%CI: 0.36-0.91； P=0.01），但与携带T等位基因的个体相比，携带C等位基因的个体患AML的风险较低（OR: 0.79, 95%CI: 0.64-0.97， P=0.03）。另外两个snp rs6087990和rs6119954在研究人群中与AML风险无显著关联。rs6087990、rs1569686、rs6119954和rs2424908的CGGT、CTAT、TGAT和CGAT单倍型似乎显著增加AML风险，而TTGC单倍型似乎显著降低风险。这些结果表明，DNMT3B多态性可能与AML的遗传易感性有关；特别是，rs1569686的G等位基因是AML的危险因素，而rs2424908的C等位基因是潜在的保护因素。
DNMT3B plays a crucial role in the generation of aberrant methylation during carcinogenesis. Polymorphisms in the DNMT3B gene may influence the DNA methylation enzymatic activity of DNMT3B, thereby modulating the susceptibility to AML. Thus, we investigated the association between SNPs in the DNMT3Bgene and their haplotypes with the risk of AML in the Chinese Han population. The DNMT3B genotype was determined by HRM in 317 de novo AML patients and 406 healthy control subjects matched for age and gender. Among the 5 SNPs investigated in this study, rs2424913 demonstrated no polymorphisms in the Chinese Han populations, rs1569686 and rs2424908 were significantly associated with AML risk. The GG genotype of rs1569686 was associated with increased AML risk (OR: 5.76; 95%CI: 2.60-12.73; P<0.01) compared with the TT genotype, and individuals with a G allele had a significantly increased risk (OR: 1.89; 95%CI: 1.41-2.52; P<0.01) for AML compared with those harboring a C allele, this polymorphism can predict the risk of AML in a minority of patients. While the CC genotype of rs2424908 appeared to reduce the AML risk (OR: 0.57; 95%CI: 0.36-0.91; P=0.01) compared with the TT genotype, individuals with a C allele were associated with a lower risk (OR: 0.79, 95%CI: 0.64-0.97, P=0.03) for developing AML compared with those harboring a T allele. The other 2 SNPs, rs6087990 and rs6119954, had no significant association with AML risk in the study population. The CGGT, CTAT, TGAT, and CGAT haplotypes of rs6087990, rs1569686, rs6119954, and rs2424908 appeared to significantly increase the AML risk, and the TTGC haplotype appeared to significantly reduce the risk. These results suggest that DNMT3B polymorphisms may contribute to the genetic susceptibility to AML; in particular, the G allele of rs1569686 serves as a risk factor for AML, whereas the C allele of rs2424908 represents a potential protective factor.
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DOI：
10.3324/haematol.2011.058305
发表时间：
2012-09-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Gronbaek, Kirsten;Mueller-Tidow, Carsten;Schlegelberger, Brigitte
通讯作者：
Schlegelberger, Brigitte
影响因子：
3.5
作者：
Khorshied, Mervat Mamdooh;El-Ghamrawy, Mona Kamal
通讯作者：
El-Ghamrawy, Mona Kamal
影响因子：
11.2
作者：
Wang, Jie;Walsh, Garret;Mao, Li
通讯作者：
Mao, Li
影响因子：
2.8
作者：
Bao, Qian;He, Bangshun;Wang, Shukui
通讯作者：
Wang, Shukui
影响因子：
3.5
作者：
Bestor, TH
通讯作者：
Bestor, TH