Role of the MDM2 Promoter Polymorphism (-309T&gt;G) in Acute Myeloid Leukemia Development

Cingeetham, Anuradha; Vuree, Sugunakar; Jiwatani, Sangeeta; Kagita, Sailaja; Dunna, Nageswara Rao; Meka, Phanni Bhushann; Gorre, Manjula; Annamaneni, Sandhya; Digumarti, Raghunadharao; Sinha, Sudha; Satti, Vishnupriya

doi:10.7314/apjcp.2015.16.7.2707

Cited by 4 publications

(2 citation statements)

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“…Previous studies on associations between MDM2 SNP309 and AML risk provided inconsistent results, and most of these studies involved less than a few hundred AML cases [14,15,16,8,9], which is insufficient to reliably assess any genetic effects. As such, we performed this meta-analysis to provide up-to-date clinical evidence for adopting MDM2 SNP309 as a prognostic biomarker in patients with AML.…”

Section: Introductionmentioning

confidence: 95%

“…Found that theMDM2 309 T/G polymorphism is associated with increased risk of bladder cancer. Anuradh et al [14] found that presence of MDM2 309 G/G genotype at promoter region increased MDM2 gene expression, hence inhibiting the p53 stress response resulting in leukemic cell transformation. Further, their study indicated that the over expression of MDM2 may lead to cell vulnerability to chemotherapy due to p53 degradation.…”

Section: Introductionmentioning

confidence: 99%

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MDM2 309 T/ G Polymorphism Is Associated With Acute Myeloid Leukemia: A Meta- Analysis

Lu¹,

Tang²,

Luo³

2017

IJSRET

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Objective:The 309 T/G polymorphism of murine double minute 2 (MDM2) gene is associated with acute myeloid leukemia, but conflicting results have been reported. In this study, we performed a meta-analysis to estimate the association between MDM2 309 T/G polymorphism and acute myeloid leukemia risk.Methods: Electronic search of PubMed was conducted to select case-control studies that contain available genotype frequencies of the MDM2 309 T/G polymorphism. Pooled Odds Ratio (OR) with 95% Confidence Interval (CI) was used to assess the strength of the association.Results: Six case-control studies, which consist of 1121 cases and 3974 controls, were identified. After pooling all the eligible studies in the meta-analysis, we found that the MDM2 309 T/G polymorphism was significantly associated with risk of acute myeloid leukemia (Recessive model G/G versus T-carriers: OR=1.738, 95% CI: 1.424 -2.122, p= 0.000; additive model G versus T: OR = 1.298, 95% CI: 1.159-1.453, p= 0.000). Symmetrical funnel plot derived from Egger's test (P=0.970) and Begg's test (P=0.851) indicated the lack of publication bias.Discussion: This meta-analysis suggests that individuals with T/G or G/G genotype of MDM2 SNP309 were significantly associated with increased acute myeloid leukemia risk. To draw comprehensive and true conclusions, well-designed studies with large sample sizes and representing different ethnicities are required.

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Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

MDM2 309 T/ G Polymorphism Is Associated With Acute Myeloid Leukemia: A Meta- Analysis

Lu¹,

Tang²,

Luo³

2017

IJSRET

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Genetic variants in HLA-DP/DQ contribute to risk of acute myeloid leukemia: A case-control study in Chinese

Cao

Qian

et al. 2020

Pathology - Research and Practice

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Mesothelin promoter variants are associated with increased soluble mesothelin-related peptide levels in asbestos-exposed individuals

et al. 2017

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Soluble-Mesothelin Related Peptide (SMRP) is a promising diagnostic biomarker for malignant pleural mesothelioma (MPM), but various confounders hamper its usefulness in surveillance programs. We previously showed that a single nucleotide polymorphism (SNP) within the 3'untranslated region (3'UTR) of mesothelin (MSLN) gene could affect the levels of SMRP. Here, we focused on SNPs located within MSLN promoter and found a strong association between serum SMRP and variant alleles of rs3764247, rs3764246 (that is in strong linkage disequilibrium with rs2235504), and rs2235503 in non-MPM subjects. The inclusion of the genotype information led to an increase in SMRP specificity from 79.9% to 85.5%. Although not statistically significant, the MPM population showed the same trend of association. In order to study the biological role of these SNPs, the promoter region of MSLN was cloned upstream a reporter gene and the four most common haplotypes were compared in a dual luciferase assay. Rs3764247 was shown to have a functional role itself. The other SNPs were shown to interact with each other in a more complex way. Altogether, these data support the idea that SMRP performance is affected by individual (i.e. genetic) variables and that MSLN expression is influenced by SNPs located within the promoter regulatory region.

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Role of the MDM2 Promoter Polymorphism (-309T>G) in Acute Myeloid Leukemia Development

Cited by 4 publications

References 20 publications

MDM2 309 T/ G Polymorphism Is Associated With Acute Myeloid Leukemia: A Meta- Analysis

MDM2 309 T/ G Polymorphism Is Associated With Acute Myeloid Leukemia: A Meta- Analysis

Genetic variants in HLA-DP/DQ contribute to risk of acute myeloid leukemia: A case-control study in Chinese

Mesothelin promoter variants are associated with increased soluble mesothelin-related peptide levels in asbestos-exposed individuals

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