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Significant association between polymorphism of the erythropoietin gene promoter and myelodysplastic syndrome.

Ma W, Kantarjian H, Zhang K, Zhang X, Wang X, Chen C, Donahue AC, Zhang Z, Yeh CH, O'Brien S, Garcia-Manero G, Caporaso N, Landgren O, Albitar M - BMC Med. Genet. (2010)

Bottom Line: The G/G genotype of the single-nucleotide polymorphism (SNP) rs1617640 in the erythropoietin (EPO) promoter has been shown to be associated with decreased EPO expression.Clinical and follow up data were available for 112 MDS patients and 186 AML patients.Further studies are warranted to investigate the utility of screening for this marker in individuals exposed to environmental toxins or chemotherapy.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Hematology/Oncology, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA.

ABSTRACT

Background: Myelodysplastic syndrome (MDS) may be induced by certain mutagenic environmental or chemotherapeutic toxins; however, the role of susceptibility genes remains unclear. The G/G genotype of the single-nucleotide polymorphism (SNP) rs1617640 in the erythropoietin (EPO) promoter has been shown to be associated with decreased EPO expression. We examined the association of rs1617640 genotype with MDS.

Methods: We genotyped the EPO rS1617640 SNP in 189 patients with MDS, 257 with acute myeloid leukemia (AML), 106 with acute lymphoblastic leukemia, 97 with chronic lymphocytic leukemia, 353 with chronic myeloid leukemia, and 95 healthy controls.

Results: The G/G genotype was significantly more common in MDS patients (47/187; 25.1%) than in controls (6/95; 6.3%) or in patients with other leukemias (101/813; 12.4%) (all P < 0.001). Individuals with the G/G genotype were more likely than those with other genotypes to have MDS (odd ratio = 4.98; 95% CI = 2.04-12.13). Clinical and follow up data were available for 112 MDS patients and 186 AML patients. There was no correlation between EPO promoter genotype and response to therapy or overall survival in MDS or AML. In the MDS group, the GG genotype was significantly associated with shorter complete remission duration, as compared with the TT genotype (P = 0.03). Time to neutrophils recovery after therapy was significantly longer in MDS patients with the G/G genotype (P = 0.02).

Conclusions: These findings suggest a strong association between the rs1617640 G/G genotype and MDS. Further studies are warranted to investigate the utility of screening for this marker in individuals exposed to environmental toxins or chemotherapy.

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Longer time to recovery of neutrophils in patients with G/G genotype.
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Figure 1: Longer time to recovery of neutrophils in patients with G/G genotype.

Mentions: Upon correlating various clinical parameters with rs1617640 genotype, there was no correlation between genotypes and survival, response, age, performance status, cytogenetics, white blood cell count, platelet count, level of hemoglobin, creatinine, beta 2-microglobulin, blood urea nitrogen, and lactate dehydrogenase. However, we found in MDS patients that neutrophils recovery required significantly longer time if patients had the G/G genotype as compared with the other genotypes (P = 0.02) (Figure 1). In addition, the MDS group with G/G genotype (n = 22) displayed significantly shorter complete remission duration relative to patients with the T/T genotype (n = 17) (P = 0.03) (Figure 2). However, the number of patients is small since only 39 patients achieved complete response. Despite the small number, we explored the effects of covariates. In multivariate analysis incorporating cytogenetic grouping with EPO polymorphism, EPO polymorphism was no longer significant while cytogenetic grouping was independent predictor of early relapse. Irrespective, this observation suggests that the genotype of the rs1617640 EPO promoter SNP has some influence on maintaining normal hematopoiesis after therapy. It is possible that a different strategy of maintenance therapy should be considered in these patients, especially since the G/G genotype of the EPO has been linked to lower levels of EPO expression relative to the T/T genotype [7]. However, due to the small number of patients and due to the analysis of multiple parameters, a confirmation of clinical correlation in larger studies is needed to rule out overfitting.


Significant association between polymorphism of the erythropoietin gene promoter and myelodysplastic syndrome.

Ma W, Kantarjian H, Zhang K, Zhang X, Wang X, Chen C, Donahue AC, Zhang Z, Yeh CH, O'Brien S, Garcia-Manero G, Caporaso N, Landgren O, Albitar M - BMC Med. Genet. (2010)

Longer time to recovery of neutrophils in patients with G/G genotype.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2992491&req=5

Figure 1: Longer time to recovery of neutrophils in patients with G/G genotype.
Mentions: Upon correlating various clinical parameters with rs1617640 genotype, there was no correlation between genotypes and survival, response, age, performance status, cytogenetics, white blood cell count, platelet count, level of hemoglobin, creatinine, beta 2-microglobulin, blood urea nitrogen, and lactate dehydrogenase. However, we found in MDS patients that neutrophils recovery required significantly longer time if patients had the G/G genotype as compared with the other genotypes (P = 0.02) (Figure 1). In addition, the MDS group with G/G genotype (n = 22) displayed significantly shorter complete remission duration relative to patients with the T/T genotype (n = 17) (P = 0.03) (Figure 2). However, the number of patients is small since only 39 patients achieved complete response. Despite the small number, we explored the effects of covariates. In multivariate analysis incorporating cytogenetic grouping with EPO polymorphism, EPO polymorphism was no longer significant while cytogenetic grouping was independent predictor of early relapse. Irrespective, this observation suggests that the genotype of the rs1617640 EPO promoter SNP has some influence on maintaining normal hematopoiesis after therapy. It is possible that a different strategy of maintenance therapy should be considered in these patients, especially since the G/G genotype of the EPO has been linked to lower levels of EPO expression relative to the T/T genotype [7]. However, due to the small number of patients and due to the analysis of multiple parameters, a confirmation of clinical correlation in larger studies is needed to rule out overfitting.

Bottom Line: The G/G genotype of the single-nucleotide polymorphism (SNP) rs1617640 in the erythropoietin (EPO) promoter has been shown to be associated with decreased EPO expression.Clinical and follow up data were available for 112 MDS patients and 186 AML patients.Further studies are warranted to investigate the utility of screening for this marker in individuals exposed to environmental toxins or chemotherapy.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Hematology/Oncology, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA.

ABSTRACT

Background: Myelodysplastic syndrome (MDS) may be induced by certain mutagenic environmental or chemotherapeutic toxins; however, the role of susceptibility genes remains unclear. The G/G genotype of the single-nucleotide polymorphism (SNP) rs1617640 in the erythropoietin (EPO) promoter has been shown to be associated with decreased EPO expression. We examined the association of rs1617640 genotype with MDS.

Methods: We genotyped the EPO rS1617640 SNP in 189 patients with MDS, 257 with acute myeloid leukemia (AML), 106 with acute lymphoblastic leukemia, 97 with chronic lymphocytic leukemia, 353 with chronic myeloid leukemia, and 95 healthy controls.

Results: The G/G genotype was significantly more common in MDS patients (47/187; 25.1%) than in controls (6/95; 6.3%) or in patients with other leukemias (101/813; 12.4%) (all P < 0.001). Individuals with the G/G genotype were more likely than those with other genotypes to have MDS (odd ratio = 4.98; 95% CI = 2.04-12.13). Clinical and follow up data were available for 112 MDS patients and 186 AML patients. There was no correlation between EPO promoter genotype and response to therapy or overall survival in MDS or AML. In the MDS group, the GG genotype was significantly associated with shorter complete remission duration, as compared with the TT genotype (P = 0.03). Time to neutrophils recovery after therapy was significantly longer in MDS patients with the G/G genotype (P = 0.02).

Conclusions: These findings suggest a strong association between the rs1617640 G/G genotype and MDS. Further studies are warranted to investigate the utility of screening for this marker in individuals exposed to environmental toxins or chemotherapy.

Show MeSH
Related in: MedlinePlus