Contributions
Abstract: PB1618
Type: Publication Only
Session title: Myelodysplastic syndromes - Biology & Translational Research
Background
Cytokine and cytokine receptors are important regulators of hematopoiesis. Overexpression of cytokine are observed in multiple myeloid diseases such as myelodysplastic syndrome (MDS). Glutathione S-transferases (GST) modulate the effects of exposure to various cytotoxic and genotoxic agents, including those associated with increased risks of the myelodysplastic syndrome. Polymorphisms in carcinogen-metabolizing genes may affect enzyme activity and subsequently influence carcinogen activation.
Aims
The aim of this study was to assess the features of alleles and genotypes distributions of GSTM1, GSTT1 and cytokine genes in MDS patients.
Methods
Thirty-nine patients with MDS (17 men and 22 women, mean age 62.4 yrs) and 150 healthy controls (HC) (cancer-free 102 men and 48 women, mean age 52.1 yrs) from North-Western Russia were genotyped for the GSTM1, GSTT1, IL-6 G174C, TNF-α G308A, IL-1β T31C polymorphisms by PCR and PCR-RFLP technique. The differences in allele and genotype frequencies between patient and HC groups were assessed by Fisher’s exact test with computation of odds ratios (OR), their 95% confidence intervals (CI) and p-values.
Results
The frequencies of the null alleles GSTM1 and GSTT1 differed slightly in both patients with MDS and in the control group. At the same time, the simultaneous presence of the IL-6 174C allele and GSTM1 null allele was more often detected in male MDS group compared to male HC group (58.8% vs. 26.4%, OR=3.9, 95%CI: 1.4-11.5, p=0.011), in female MDS patients was not different to female HC group (36.3%, vs. 33.3%, respectively). The frequency of the IL-1β 31C allele in patients MDS with GSTM1 null allele was nearly 2-fold higher, than in those HC group (41% vs 23,3 % respectively, OR=2.3, 95% CI: 1.1-4.8, p=0.04), In contrast, IL-1β 31C allele was observed 5.5 -fold higher in men HC group compared in men MDS group with undeleted GSTM1 allele (33.3% vs 5,9 %, OR=8.0, 95% CI: 1.0-63.0, p=0.022). At availability genotype IL-6 174CC with GSTT1 null allele in the male patients MDS were found more often than the same male group HC (11,8% vs 1%, OR=13.5, 95% CI: 1.1-157, p=0.053, respectively). Genotype IL-1β T31C in the presence undeleted GSTT1 allele was more often in female MDS group compared to female HC group (50% vs. 22,9%, OR=3.4, 95%CI: 1.1-9.8, p=0.03). TNF-α G308A polymorphism in patients were not statistically different from those in HC group.
Conclusion
We believe that the distribution of alleles and genotypes of the GSTM1, GSTT1 and cytokine genes in patients with MDS is multifactorial and requires further study to identify risk factors for the development of the disease and explain the causes of their occurrence.
Keyword(s): Gene polymorphism, MDS
Abstract: PB1618
Type: Publication Only
Session title: Myelodysplastic syndromes - Biology & Translational Research
Background
Cytokine and cytokine receptors are important regulators of hematopoiesis. Overexpression of cytokine are observed in multiple myeloid diseases such as myelodysplastic syndrome (MDS). Glutathione S-transferases (GST) modulate the effects of exposure to various cytotoxic and genotoxic agents, including those associated with increased risks of the myelodysplastic syndrome. Polymorphisms in carcinogen-metabolizing genes may affect enzyme activity and subsequently influence carcinogen activation.
Aims
The aim of this study was to assess the features of alleles and genotypes distributions of GSTM1, GSTT1 and cytokine genes in MDS patients.
Methods
Thirty-nine patients with MDS (17 men and 22 women, mean age 62.4 yrs) and 150 healthy controls (HC) (cancer-free 102 men and 48 women, mean age 52.1 yrs) from North-Western Russia were genotyped for the GSTM1, GSTT1, IL-6 G174C, TNF-α G308A, IL-1β T31C polymorphisms by PCR and PCR-RFLP technique. The differences in allele and genotype frequencies between patient and HC groups were assessed by Fisher’s exact test with computation of odds ratios (OR), their 95% confidence intervals (CI) and p-values.
Results
The frequencies of the null alleles GSTM1 and GSTT1 differed slightly in both patients with MDS and in the control group. At the same time, the simultaneous presence of the IL-6 174C allele and GSTM1 null allele was more often detected in male MDS group compared to male HC group (58.8% vs. 26.4%, OR=3.9, 95%CI: 1.4-11.5, p=0.011), in female MDS patients was not different to female HC group (36.3%, vs. 33.3%, respectively). The frequency of the IL-1β 31C allele in patients MDS with GSTM1 null allele was nearly 2-fold higher, than in those HC group (41% vs 23,3 % respectively, OR=2.3, 95% CI: 1.1-4.8, p=0.04), In contrast, IL-1β 31C allele was observed 5.5 -fold higher in men HC group compared in men MDS group with undeleted GSTM1 allele (33.3% vs 5,9 %, OR=8.0, 95% CI: 1.0-63.0, p=0.022). At availability genotype IL-6 174CC with GSTT1 null allele in the male patients MDS were found more often than the same male group HC (11,8% vs 1%, OR=13.5, 95% CI: 1.1-157, p=0.053, respectively). Genotype IL-1β T31C in the presence undeleted GSTT1 allele was more often in female MDS group compared to female HC group (50% vs. 22,9%, OR=3.4, 95%CI: 1.1-9.8, p=0.03). TNF-α G308A polymorphism in patients were not statistically different from those in HC group.
Conclusion
We believe that the distribution of alleles and genotypes of the GSTM1, GSTT1 and cytokine genes in patients with MDS is multifactorial and requires further study to identify risk factors for the development of the disease and explain the causes of their occurrence.
Keyword(s): Gene polymorphism, MDS