[The C46359T polymorphism of DNMT3B promoter gene and pathogenesis of acute leukemia].
ABSTRACT To explore the relationship between the polymorphism of C46359T in DNMT3B promoter and the pathogenesis of acute leukemia (AL).
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.
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.
Different distribution of genotypes in different races, the CT heterozygote was relative to the pathogenesis of AL.
- SourceAvailable from: Agustin F Fernandez[show abstract] [hide abstract]
ABSTRACT: Epigenetic mechanisms play an important role in gene regulation during development. DNA methylation, which is probably the most important and best-studied epigenetic mechanism, can be abnormally regulated in common pathologies, but the origin of altered DNA methylation remains unknown. Recent research suggests that these epigenetic alterations could depend, at least in part, on genetic mutations or polymorphisms in DNA methyltransferases and certain genes encoding enzymes of the one-carbon metabolism pathway. Indeed, the de novo methyltransferase 3B (DNMT3B) has been recently found to be mutated in several types of cancer and in the immunodeficiency, centromeric region instability and facial anomalies syndrome (ICF), in which these mutations could be related to the loss of global DNA methylation. In addition, mutations in glycine-N-methyltransferase (GNMT) could be associated with a higher risk of hepatocellular carcinoma and liver disease due to an unbalanced S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) ratio, which leads to aberrant methylation reactions. Also, genetic variants of chromatin remodeling proteins and histone tail modifiers are involved in genetic disorders like α thalassemia X-linked mental retardation syndrome, CHARGE syndrome, Cockayne syndrome, Rett syndrome, systemic lupus erythematous, Rubinstein-Taybi syndrome, Coffin-Lowry syndrome, Sotos syndrome, and facioescapulohumeral syndrome, among others. Here, we review the potential genetic alterations with a possible role on epigenetic factors and discuss their contribution to human disease.Cellular and Molecular Life Sciences CMLS 03/2013; · 5.62 Impact Factor