Original Article The polymorphism and whole-genome DNA methylation level of DNMT1 gene in acute leukemia children

Xuepeng He, Peng Chen, Kai Yang, Bing Liu, Yuan Zhang, Fang Wang, Zhi Guo, Xiaodong Liu, Jinxing Lou, Huiren Chen
2017 Int J Clin Exp Med   unpublished
Acute leukemia (AL) is the most popular malignant tumor in children. Currently little has been known about the relationship between childhood AL pathogenesis and whole-genome methylation level. As the polymor-phism of DNA methyltransferase (DNMT) gene can affect DNA methylation level, we investigated the whole genome methylation level in childhood AL patients. Meanwhile, the relationship between DNMT1 gene polymorphism and susceptibility of childhood AL was also been investigated. A
more » ... study was performed recruiting childhood AL patients and age-matched healthy children (N=168 each). PCR-ligase detective response (PCR-LDR) typing method was used to study the genotype distribution of human DNMT1 gene at rs2228611 and rs10854076 loci. Pyrophosphate sequencing was used to measure LINE-1 methylation level. Allele frequency of two loci fits Hardy-Weinberg equilibrium (P>0.05). Significant difference of genotype and allele frequency existed at locus rs10854076 but not locus rs2228611 between patients and healthy people. Allele C was found to be a risk factor for AL. A significant difference of LINE-1 methylation level existed between the two groups, as AL patients had lower methylation level (P<0.05). Specifically, LINE-1 methylation level at locus rs10854076 but not at rs2228611 had significant difference between patients and controls. Polymorphism of DNMT1 gene at locus rs10854076 is related with children AL susceptibility, possibly via affecting LINE-1 methylation level.