ASSOCIATION BETWEEN POLYMORPHISM OF FOLATE AND METHIONINE METABOLISM GENES AND ABERRANT DNA METHYLATION IN PATIENTS WITH ACUTE MYELOID LEUKEMIA AND MYELODYSPLASTIC SYNDROME
(Abstract release date: 05/19/16)
EHA Library. Sidorova Z. 06/09/16; 134541; PB1641
Dr. Zhanna Sidorova
Contributions
Contributions
Abstract
Abstract: PB1641
Type: Publication Only
Background
Aberrant DNA methylation of tumor-supressor genes may be involved in the development of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Polymorphism of folate and methionine metabolism (FMM) related genes can influence the methylation processes and, therefore, operated on both AML and MDS development.
Aims
The aim of this study was to assess the association between polymorphism of FMM related genes and aberrant methylation of promoter regions of several tumor supressor genes in AML and MDS patients.
Methods
Fifty-seven patients with AML (20 men and 37 women, mean age 51.0 yrs) and 51 patients with MDS (24 men and 27 women, mean age 62.4 yrs) were genotyped for the MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G and MTHFD G1958A polymorphisms by PCR-RFLP technique. The differences in allele and genotype frequencies were assessed by Fisher’s exact test with computation of odds ratios (OR), their 95% confidence intervals (CI) and p-values. Methylation-specific PCR was used to study the methylation status of promoter regions of SOX7, p15INK4b, SFRP1, SFRP4 and SFRP5 genes.
Results
Thirty patients AML (10 men and 20 women) and 21 patients MDS (9 men and 12 women) had aberrant methylation of 0-2 genes (0-2 MG group AML and MDS respectively). Twenty seven patients AML (10 men and 17 women) and 30 patients MDS (15 men and 15 women) had aberrant methylation of 3-5 genes (3-5 MG group AML and MDS respectively).In MDS group, hypermethylation of all 5 genes was found in 5 men and was not found in female patients (20.8% vs. 0.0%, respectively, OR=15.5, 95%CI: 0.8-297.0, p=0.02). At the same time, aberrant methylation of all 5 genes was found in 8 AML patients (4 men and 4 women, 20.0% vs. 10.8%, respectively, OR=1.9, 95%CI: 0.4-8.2, p=0.45).The presence of the MTHFR 1298C allele was increased in male patients AML from the group 0-2 MG when compared to male MDS patients in the 0-2 MG group (73% vs. 43%, respectively, OR=3.7, 95%CI: 1.1-11.9, p=0.042).The presence of the MTHFR 677T allele was increased in female AML patients from the group 3-5 MG when compared to female AML patients in the 0-2 MG group (76.5% vs. 35.0%, respectively, OR=6.0, 95%CI: 1.4-25.7, p=0.02), but was not different between women from 3-5 MG and 0-2 MG groups MDS patients (46.7% vs. 33.4 %, respectively, OR=1.8, 95%CI: 0.4-8.4, p=0.7). It is interesting, that positivity for the MTHFR 677T allele was significantly increased in male MDS patients from the group 0-2 MG when compared to male 3-5 MG group (100.0% vs. 46.7%, respectively, OR=21.5, 95%CI: 1.2-437, p=0.01).In male patients with MDS, the MTHFD 1958 AA genotype was more frequently seen in the group 3-5 MG than in the group 0-2 MG (33.0% vs. 0.0%, respectively, OR=9.9, 95%CI: 0.5-205.0, p=0.12). This genotype was also overrepresented in the group 3-5 MG of women with AML when compared to group 0-2 MG of female AML patients (29.4% vs. 5.0%, respectively, OR=7.9, 95%CI: 0.8-76.3, p=0.08).
Conclusion
We conclude that polymorphism of the FMM genes could have an important role in mechanism of epigenetic disturbances at AML and MDS, associated with aberrant methylation of CpG islands of tumor-supressor genes.
Session topic: E-poster
Keyword(s): AML, Genetic polymorphism, MDS, Methylation
Type: Publication Only
Background
Aberrant DNA methylation of tumor-supressor genes may be involved in the development of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Polymorphism of folate and methionine metabolism (FMM) related genes can influence the methylation processes and, therefore, operated on both AML and MDS development.
Aims
The aim of this study was to assess the association between polymorphism of FMM related genes and aberrant methylation of promoter regions of several tumor supressor genes in AML and MDS patients.
Methods
Fifty-seven patients with AML (20 men and 37 women, mean age 51.0 yrs) and 51 patients with MDS (24 men and 27 women, mean age 62.4 yrs) were genotyped for the MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G and MTHFD G1958A polymorphisms by PCR-RFLP technique. The differences in allele and genotype frequencies were assessed by Fisher’s exact test with computation of odds ratios (OR), their 95% confidence intervals (CI) and p-values. Methylation-specific PCR was used to study the methylation status of promoter regions of SOX7, p15INK4b, SFRP1, SFRP4 and SFRP5 genes.
Results
Thirty patients AML (10 men and 20 women) and 21 patients MDS (9 men and 12 women) had aberrant methylation of 0-2 genes (0-2 MG group AML and MDS respectively). Twenty seven patients AML (10 men and 17 women) and 30 patients MDS (15 men and 15 women) had aberrant methylation of 3-5 genes (3-5 MG group AML and MDS respectively).In MDS group, hypermethylation of all 5 genes was found in 5 men and was not found in female patients (20.8% vs. 0.0%, respectively, OR=15.5, 95%CI: 0.8-297.0, p=0.02). At the same time, aberrant methylation of all 5 genes was found in 8 AML patients (4 men and 4 women, 20.0% vs. 10.8%, respectively, OR=1.9, 95%CI: 0.4-8.2, p=0.45).The presence of the MTHFR 1298C allele was increased in male patients AML from the group 0-2 MG when compared to male MDS patients in the 0-2 MG group (73% vs. 43%, respectively, OR=3.7, 95%CI: 1.1-11.9, p=0.042).The presence of the MTHFR 677T allele was increased in female AML patients from the group 3-5 MG when compared to female AML patients in the 0-2 MG group (76.5% vs. 35.0%, respectively, OR=6.0, 95%CI: 1.4-25.7, p=0.02), but was not different between women from 3-5 MG and 0-2 MG groups MDS patients (46.7% vs. 33.4 %, respectively, OR=1.8, 95%CI: 0.4-8.4, p=0.7). It is interesting, that positivity for the MTHFR 677T allele was significantly increased in male MDS patients from the group 0-2 MG when compared to male 3-5 MG group (100.0% vs. 46.7%, respectively, OR=21.5, 95%CI: 1.2-437, p=0.01).In male patients with MDS, the MTHFD 1958 AA genotype was more frequently seen in the group 3-5 MG than in the group 0-2 MG (33.0% vs. 0.0%, respectively, OR=9.9, 95%CI: 0.5-205.0, p=0.12). This genotype was also overrepresented in the group 3-5 MG of women with AML when compared to group 0-2 MG of female AML patients (29.4% vs. 5.0%, respectively, OR=7.9, 95%CI: 0.8-76.3, p=0.08).
Conclusion
We conclude that polymorphism of the FMM genes could have an important role in mechanism of epigenetic disturbances at AML and MDS, associated with aberrant methylation of CpG islands of tumor-supressor genes.
Session topic: E-poster
Keyword(s): AML, Genetic polymorphism, MDS, Methylation
Abstract: PB1641
Type: Publication Only
Background
Aberrant DNA methylation of tumor-supressor genes may be involved in the development of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Polymorphism of folate and methionine metabolism (FMM) related genes can influence the methylation processes and, therefore, operated on both AML and MDS development.
Aims
The aim of this study was to assess the association between polymorphism of FMM related genes and aberrant methylation of promoter regions of several tumor supressor genes in AML and MDS patients.
Methods
Fifty-seven patients with AML (20 men and 37 women, mean age 51.0 yrs) and 51 patients with MDS (24 men and 27 women, mean age 62.4 yrs) were genotyped for the MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G and MTHFD G1958A polymorphisms by PCR-RFLP technique. The differences in allele and genotype frequencies were assessed by Fisher’s exact test with computation of odds ratios (OR), their 95% confidence intervals (CI) and p-values. Methylation-specific PCR was used to study the methylation status of promoter regions of SOX7, p15INK4b, SFRP1, SFRP4 and SFRP5 genes.
Results
Thirty patients AML (10 men and 20 women) and 21 patients MDS (9 men and 12 women) had aberrant methylation of 0-2 genes (0-2 MG group AML and MDS respectively). Twenty seven patients AML (10 men and 17 women) and 30 patients MDS (15 men and 15 women) had aberrant methylation of 3-5 genes (3-5 MG group AML and MDS respectively).In MDS group, hypermethylation of all 5 genes was found in 5 men and was not found in female patients (20.8% vs. 0.0%, respectively, OR=15.5, 95%CI: 0.8-297.0, p=0.02). At the same time, aberrant methylation of all 5 genes was found in 8 AML patients (4 men and 4 women, 20.0% vs. 10.8%, respectively, OR=1.9, 95%CI: 0.4-8.2, p=0.45).The presence of the MTHFR 1298C allele was increased in male patients AML from the group 0-2 MG when compared to male MDS patients in the 0-2 MG group (73% vs. 43%, respectively, OR=3.7, 95%CI: 1.1-11.9, p=0.042).The presence of the MTHFR 677T allele was increased in female AML patients from the group 3-5 MG when compared to female AML patients in the 0-2 MG group (76.5% vs. 35.0%, respectively, OR=6.0, 95%CI: 1.4-25.7, p=0.02), but was not different between women from 3-5 MG and 0-2 MG groups MDS patients (46.7% vs. 33.4 %, respectively, OR=1.8, 95%CI: 0.4-8.4, p=0.7). It is interesting, that positivity for the MTHFR 677T allele was significantly increased in male MDS patients from the group 0-2 MG when compared to male 3-5 MG group (100.0% vs. 46.7%, respectively, OR=21.5, 95%CI: 1.2-437, p=0.01).In male patients with MDS, the MTHFD 1958 AA genotype was more frequently seen in the group 3-5 MG than in the group 0-2 MG (33.0% vs. 0.0%, respectively, OR=9.9, 95%CI: 0.5-205.0, p=0.12). This genotype was also overrepresented in the group 3-5 MG of women with AML when compared to group 0-2 MG of female AML patients (29.4% vs. 5.0%, respectively, OR=7.9, 95%CI: 0.8-76.3, p=0.08).
Conclusion
We conclude that polymorphism of the FMM genes could have an important role in mechanism of epigenetic disturbances at AML and MDS, associated with aberrant methylation of CpG islands of tumor-supressor genes.
Session topic: E-poster
Keyword(s): AML, Genetic polymorphism, MDS, Methylation
Type: Publication Only
Background
Aberrant DNA methylation of tumor-supressor genes may be involved in the development of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Polymorphism of folate and methionine metabolism (FMM) related genes can influence the methylation processes and, therefore, operated on both AML and MDS development.
Aims
The aim of this study was to assess the association between polymorphism of FMM related genes and aberrant methylation of promoter regions of several tumor supressor genes in AML and MDS patients.
Methods
Fifty-seven patients with AML (20 men and 37 women, mean age 51.0 yrs) and 51 patients with MDS (24 men and 27 women, mean age 62.4 yrs) were genotyped for the MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G and MTHFD G1958A polymorphisms by PCR-RFLP technique. The differences in allele and genotype frequencies were assessed by Fisher’s exact test with computation of odds ratios (OR), their 95% confidence intervals (CI) and p-values. Methylation-specific PCR was used to study the methylation status of promoter regions of SOX7, p15INK4b, SFRP1, SFRP4 and SFRP5 genes.
Results
Thirty patients AML (10 men and 20 women) and 21 patients MDS (9 men and 12 women) had aberrant methylation of 0-2 genes (0-2 MG group AML and MDS respectively). Twenty seven patients AML (10 men and 17 women) and 30 patients MDS (15 men and 15 women) had aberrant methylation of 3-5 genes (3-5 MG group AML and MDS respectively).In MDS group, hypermethylation of all 5 genes was found in 5 men and was not found in female patients (20.8% vs. 0.0%, respectively, OR=15.5, 95%CI: 0.8-297.0, p=0.02). At the same time, aberrant methylation of all 5 genes was found in 8 AML patients (4 men and 4 women, 20.0% vs. 10.8%, respectively, OR=1.9, 95%CI: 0.4-8.2, p=0.45).The presence of the MTHFR 1298C allele was increased in male patients AML from the group 0-2 MG when compared to male MDS patients in the 0-2 MG group (73% vs. 43%, respectively, OR=3.7, 95%CI: 1.1-11.9, p=0.042).The presence of the MTHFR 677T allele was increased in female AML patients from the group 3-5 MG when compared to female AML patients in the 0-2 MG group (76.5% vs. 35.0%, respectively, OR=6.0, 95%CI: 1.4-25.7, p=0.02), but was not different between women from 3-5 MG and 0-2 MG groups MDS patients (46.7% vs. 33.4 %, respectively, OR=1.8, 95%CI: 0.4-8.4, p=0.7). It is interesting, that positivity for the MTHFR 677T allele was significantly increased in male MDS patients from the group 0-2 MG when compared to male 3-5 MG group (100.0% vs. 46.7%, respectively, OR=21.5, 95%CI: 1.2-437, p=0.01).In male patients with MDS, the MTHFD 1958 AA genotype was more frequently seen in the group 3-5 MG than in the group 0-2 MG (33.0% vs. 0.0%, respectively, OR=9.9, 95%CI: 0.5-205.0, p=0.12). This genotype was also overrepresented in the group 3-5 MG of women with AML when compared to group 0-2 MG of female AML patients (29.4% vs. 5.0%, respectively, OR=7.9, 95%CI: 0.8-76.3, p=0.08).
Conclusion
We conclude that polymorphism of the FMM genes could have an important role in mechanism of epigenetic disturbances at AML and MDS, associated with aberrant methylation of CpG islands of tumor-supressor genes.
Session topic: E-poster
Keyword(s): AML, Genetic polymorphism, MDS, Methylation
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