Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme involved in folate metabolism, DNA methylation and synthesis. We investigated the association between MTHFR polymorphisms and the risks of acute and chronic leukaemias. MTHFR C677T and A1298C were genotyped in 396 Korean individuals using multiplex polymerase chain reaction/restriction fragment-length polymorphism. They were acute lymphoblastic leukaemia (ALL, n = 89), acute myeloid leukaemia (AML, n = 55), biphenotypic acute leukaemia (n = 12), chronic myelogenous leukaemia (CML, n = 40), and normal controls (n = 200). C677T genotypes were not associated with the risk of each disease. A1298C variants, however, significantly decreased the risks of ALL and CML compared with 1298AA. Odds ratios and 95% confidence intervals of 1298AC and 1298AC + CC were 0.53 (0.31-0.93) and 0.54 (0.31-0.93) in ALL, and 0.34 (0.14-0.80) and 0.40 (0.18-0.89) in CML, respectively, compared with 1298AA. These findings demonstrate that the development of ALL and CML is more dependent on folate status, and more susceptible to DNA instability than that of AML. In addition, A1298C rather than C677T may be a more important genetic risk modifier in leukaemogenesis at least in the Korean population.
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PMID:Methylenetetrahydrofolate reductase A1298C genotypes are associated with the risks of acute lymphoblastic leukaemia and chronic myelogenous leukaemia in the Korean population. 1670 30

Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in folate metabolism and DNA methylation. Studies on MTHFR polymorphism in leukemia have largely focused on the protective role of MTHFR polymorphism in acute lymphoblastic leukemia (ALL). We evaluated the C677T and A1298C polymorphisms using the TaqMan allelic discrimination assay in various malignancies. The study population included 115 subjects with chronic myelogenous leukemia (CML), 200 with acute myelogenous leukemia (AML), 196 with multiple myeloma (MM) and 434 healthy control subjects. The frequency of 1298CC was statistically significantly higher in subjects with CML than that of the controls (OR=5.12, 95% CI: 1.75-14.9, P-value=.003). Of note, the frequencies of 677CC/1298CC genotype were statistically significantly higher in subjects with CML, AML and MM than that of the controls (OR=8.8, 3.5, 3.83, P-value=.002, 0.036, 0.023, respectively). Our results demonstrate that the MTHFR 1298CC homozygote variant is strongly associated with an increased risk of CML, while MTHFR C677T does not significantly affect the risk of CML. Moreover, we demonstrated that MTHFR 677CC and 1298CC genotype might have combined effect on risk of CML, AML and MM and it is inferred that the A1298C may play a different role in carcinogenesis, depending on the types of organs involved, the types of disease entities and the genotype of C677T.
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PMID:MTHFR 677CC/1298CC genotypes are highly associated with chronic myelogenous leukemia: a case-control study in Korea. 1715 40

The aim of this study was to set up a new method for 5, 10-Methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms (SNP) genotyping, and to investigate the hereditary susceptibility of hematological malignancy. Prepared an aimed gene microarray based on cDNA microarray theory, dual-color fluorescence hybridization was used to detect SNP loci, and DNA sequencing was performed to confirm the results. The MTHFR C677T SNP loci of 157 controls and 127 patients with hematological malignancies (30 multiple myeloma, 28 non-Hodgkin's lymphoma, 22 acute lymphoblastic leukemia, 40 acute myeloid leukemia, 7 chronic myeloid leukemia) from Jiangsu province were detected. The results showed that after overlapping, homozygous wild type, heterozygote type and homozygous mutant type yielded green, yellow and red fluorescence, respectively. DNA sequencing validated these results. The allele frequency of 677C and 677T in patients and controls were 58.7% and 66.9%, 41.3% and 33.1% respectively, showing statistically significant difference (chi2 = 4.077, P = 0.043). 677TT genotype showed a significantly higher risk of MM (OR = 4.21; 95% CI = 1.50 - 11.83; P = 0.006). It is concluded that this microarray-based method is accurate, high-throughput and inexpensive, suitable for SNP genotyping in a large number of individuals. C677T polymorphisms influence the risk of hematological malignancies. 677TT genotype is susceptive to MM.
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PMID:[A new method for 5, 10-methylenetetrahydrofolate reductase single nucleotide polymorphisms genotyping used to study susceptibility of hematological malignancy]. 1720 66

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating the intracellular folate metabolism which plays an important role in carcinogenesis through DNA methylation and nucleotide synthesis. The common MTHFR single nucleotide polymorphism C677T has been reported to be associated with reduced enzymatic activity. In order to investigate the influence of this polymorphism on the risk of chronic myeloid leukemia (CML), we performed a case-control study in a Serbian population of 52 patients with CML and 53 healthy control subjects. MTHFR C677T polymorphism genotyping was assessed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The results demonstrated no statistical difference in MTHFR 677 frequency distribution between patient and control groups. Our findings suggest that MTHFR 677 gene variants have no significant influence on the susceptibility to CML in a Serbian population.
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PMID:Association between methylenetetrahydrofolate reductase polymorphism C677T and risk of chronic myeloid leukemia in Serbian population. 2213 38

Methylenetetrahydrofolate reductase (MTHFR) gene plays a pivotal role in folate metabolism. Several genetic variations in MTHFR gene as MTHFR-C677T and MTHFR-A1298C result in decreased MTHFR activity, which could influence efficient DNA methylation and explain susceptibility to different cancers. The etiology of chronic myeloid leukemia (CML) is obscure and little is known about individual's susceptibility to CML. In order to assess the influence of these genetic polymorphisms on the susceptibility to CML and its effect on the course of the disease among Egyptians, we performed an age-gender-ethnic matched case-control study. The study included 97 CML patients and 130 healthy controls. Genotyping of MTHFR-C677T and -A1298C was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The results showed no statistical difference in the distribution of MTHFR-C677T and -A1298C polymorphic genotypes between CML patients and controls. The frequency of MTHFR 677-TT homozygous variant was significantly higher in patients with accelerated/blastic transformation phase when compared to those in the chronic phase of the disease. In conclusion, our study revealed that MTHFR-C677T and -A1298C polymorphisms could not be considered as genetic risk factors for CML in Egyptians. However, MTHFR 677-TT homozygous variant might be considered as a molecular predictor for disease progression.
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PMID:Methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in chronic myeloid leukemia: an Egyptian study. 2449 63

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating the intracellular folate metabolism which plays an important role in carcinogenesis through DNA methylation. We aimed to evaluate the association between MTHFR A1298C and C677T polymorphisms and the risks of chronic myeloid leukemia (CML). Eighty-five patients with CML and a control group containing 100 healthy, age and sex matched individuals were examined for MTHFR C677T and A1298C polymorphisms using polymerase chain reaction-restriction fragment-length (PCR-RFLP) method. The frequency of 677TT genotype in patients with CML was significantly higher compared to controls (OR=2.513, 95% CI: 0.722-4.086, P=0.025). No such association was shown for heterozygous 677CT (OR=1.010, 95% CI: 0.460-2.218, P=0.981). Moreover, for A1298C genotype, a statistically significant higher frequency of 1298CC was also detected in CML patients compared to control group (OR=1.1816, 95% CI: 0.952-3.573, P=0.036), 0.036). No such statistical significance was demonstrable for heterozygote 1298AC (OR=1.046, 95% CI: 0.740-1.759, P=0.092). In addition, patients with joint 677CT/1298AC or 677TT/1298CC genotypes showed an association with increased risk of CML (OR=1.849, 95% CI: 0.935-2.540, P=0.024; OR=1.915, 95% CI: 1.202-3.845, P=0.020 respectively). .A statistically significant increased risk of resistant to therapy was observed with 677CT and 1298AC genotypes (P=0.001, P=0.002 respectively). We conclude that both MTHFR 677TT and 1298CC polymorphisms have been associated with risk of CML and both 677CT and 1298AC genotypes are associated with higher risk of resistant to therapy.
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PMID:MTHFR A1298C and C677T gene polymorphisms and susceptibility to chronic myeloid leukemia in Egypt. 2496 71

Background: Methylenetetrahydrofolate reductase (MTHFR) gene is a crucial regulator of folate metabolism and its two prominent polymorphic variants C677T and A1298C lead to decreased MTHFR enzyme activity. Aim of the Study: We planned this case-control study based on numerous studies supporting the association of MTHFR polymorphisms (C677T and A1298C) with CML risk in different ethnic populations. Therefore, the influence of these polymorphisms on CML susceptibility was investigated among Kashmiri population (North India). Materials and Methods: Polymerase chain reaction/restriction fragment length polymorphism (RFLP) technique was employed for genotyping MTHFR C677T and A1298C SNP's in 125 CML patients as against 150 age and gender matched healthy controls. Results: A significant difference was observed in frequency of 677CT genotype between cases and controls [46.4 vs. 27.3% (p = 0.0005)]. Similarly combined 677CT+TT genotype showed significant difference between cases and controls [50.4 vs. 28.6% (p = 0.0002)]. Both MTHFR 677CT and 677CT+TT genotypes imposed greater than 2-fold risk of developing CML (OR = 2.4, 95%CI: 1.46-4.05; OR = 2.5, 95%CI: 1.53-4.16). In case of A1298C SNP, the frequency of 1298AC genotype was higher in controls (64.0%) as compared to CML cases (48.8%) (p = 0.04) and imparted a significant protective role from CML predisposition. Furthermore, haplotype analysis revealed only "677CT/1298AA" haplotype significantly increased the risk of CML predisposition [(p = 0.008) (OR = 3.2, 95% CI: 1.3-7.4)]. Conclusion: We conclude that both MTHFR C677T and A1298C polymorphisms may be important genetic modifiers and seem to have a plausible role to confer risk of CML in Kashmiri population, where C677T SNP strongly increases the risk of CML while as A1298C SNP has a protective effect.
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PMID:Methylenetetrahydrofolate Reductase Gene C677T and A1298C Polymorphic Sequence Variations Influences the Susceptibility to Chronic Myeloid Leukemia in Kashmiri Population. 3139 77