Luo Ying, Yu Luting, Yu Tingting, Jiang Feixia, Cai Xubing, Zhao Yilun, Pan Shiyang, Luo Chen
Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, 210029 Nanjing, China; Nanjing Red Cross Blood Center, 210003 Nanjing, China.
School of Life Science and Technology, China Pharmaceutical University, 210009 Nanjing, China.
Biomed Pharmacother. 2015 Jul;73:35-9. doi: 10.1016/j.biopha.2015.05.001. Epub 2015 May 20.
It has been suggested that aberrant DNA methylation is a common epigenetic alteration in malignancies. Genetic variations in DNA methyltransferase 1 gene (DNMT1), which encodes the maintenance methyltransferase, have been demonstrated to be involved in cancer susceptibility. In the present study, we investigated whether genetic polymorphisms in DNMT1 could be associated with risk of childhood acute lymphoblastic leukemia (ALL) in a Chinese population.
We selected seven tagging single-nucleotide polymorphisms (tagSNPs, rs11880388, rs10423341, rs7253062, rs11085721, rs2228611, rs2228612 and rs16999593) in DNMT1 and genotyped these SNPs by using TaqMan method in a case-control study of 377 patients with ALL and 500 healthy controls. The logistic regression was used to assess the genetic associations with occurrence of ALL with adjustment for possible confounders.
We found that one (rs11085721) of the seven tagSNPs was significantly associated with the risk of ALL. Compared with individuals' with DNMT1 rs11085721 GG genotype, those subjects carrying the rs11085721 GT genotypes were associated with significantly increased risk for ALL (GT vs. GG:OR=1.29, 95% CI=1.10-1.51). Similar association was also observed when combined the individuals with rs11085721 GT and rs11085721 TT genotypes (GT/TT vs. TT:OR=1.29, 95% CI=1.10-1.50). No positive results were observed for the other tagSNPs.
Our results suggest that the DNMT1 rs11085721 polymorphism may confer susceptibility to ALL in the Chinese population. The initial findings should be validated by large population-based prospective studies in the future.
有研究表明，异常的DNA甲基化是恶性肿瘤中常见的表观遗传改变。编码维持性甲基转移酶的DNA甲基转移酶1基因（DNMT1）的遗传变异已被证明与癌症易感性有关。在本研究中，我们调查了中国人群中DNMT1基因多态性是否与儿童急性淋巴细胞白血病（ALL）风险相关。
我们在DNMT1基因中选择了7个标签单核苷酸多态性（tagSNP，rs11880388、rs10423341、rs7253062、rs11085721、rs2228611、rs2228612和rs16999593），并在一项包含377例ALL患者和500名健康对照的病例对照研究中使用TaqMan方法对这些SNP进行基因分型。采用逻辑回归分析评估与ALL发生的遗传关联，并对可能的混杂因素进行校正。
我们发现7个tagSNP中的一个（rs11085721）与ALL风险显著相关。与携带DNMT1 rs11085721 GG基因型的个体相比，携带rs11085721 GT基因型的个体患ALL的风险显著增加（GT与GG：OR = 1.29，95% CI = 1.10 - 1.51）。当将rs11085721 GT和rs11085721 TT基因型个体合并时，也观察到类似的关联（GT/TT与TT：OR = 1.29，95% CI = 1.10 - 1.50）。其他tagSNP未观察到阳性结果。
我们的结果表明，DNMT1 rs11085721多态性可能使中国人群易患ALL。这一初步发现未来应通过基于大规模人群的前瞻性研究进行验证。
