Polymorphisms of the receptor for advanced glycation end products as vasculopathy predictor in sickle cell disease.

BACKGROUND: The genetic variants of the receptor for advanced glycation end products (RAGE) gene have been associated with vascular disease risk. The objective of this work was to explore the association of three single-nucleotide polymorphisms (SNPs) of RAGE gene (374T/A, 429T/C, and G82S) with vascular complications in SCD. METHODS: The study was conducted on 40 children with SCD and 40 healthy children served as controls. All participants were genotyped for the three studied RAGE polymorphisms by polymerase chain reaction (PCR). RESULTS: Regarding 374T/A polymorphism, the frequency of TA, TT genotypes and T allele were higher in patients (p < 0.001). T allele was associated with higher incidence of sickling crisis and stroke (p < 0.05). In the subgroup analyses of 429T/C polymorphism, an association between C allele and SCD vascular complications was observed (p < 0.05). Concerning the frequency of G82S genotypes of RAGE, GG variant was detected in 39 (97.5%) of the patients, as compared with 40 (100%) of controls (p = 0.3). A regression analysis proved that HbS%, serum ferritin, and the -374T and 429C alleles were significant independent predictors of frequent sickling episodes (p < 0.05). CONCLUSIONS: The C allele of -429T/C and T allele of 374T/A RAGE polymorphisms may be considered as predictors for vascular dysfunction in SCD. IMPACT: The C allele of -429T/C and T allele of 374T/A RAGE polymorphisms may be considered as predictors for vascular dysfunction in SCD patients. To our knowledge, our study is the first exploring the association of three single-nucleotide polymorphisms of RAGE gene (374T/A, 429T/C, and G82S) with vascular complications in SCD. Early identification of patients carrying these genetic variants might be of great importance not only to identify subjects at risk of vasculopathy but also to direct them to RAGE-targeted treatments.

Flow cytometry in detection of Nucleophosmin 1 mutation in acute myeloid leukemia patients: A reproducible tertiary hospital experience.

INTRODUCTION: Nucleophosmin 1 (NPM1) mutation is one of the most frequent gene mutations in adult acute myeloid leukemia (AML), being detected in 35% of all cases and in up to 60% of patients with normal karyotype AML. AML with mutated NPM1 has distinct pathology, immunophenotyping, and confirmed favorable prognostic significance. Hence, AML with mutated NPM1 is a separate entity in the revised 2016 World Health Organization classification. This study aimed to evaluate the use of a reproducible flow cytometry approach in the assay of mutant NPM1 protein in AML patients and to correlate flow cytometric results with the NPM1 gene mutation. METHODS: Eighty-nine newly diagnosed AML patients were evaluated for the expression of mutant NPM1 using flow cytometry and for the presence of NPM1 exon 12 mutations using high-resolution melting polymerase chain reaction (HRM PCR). RESULTS: The NPM1 mutation was found in 35 (39.3%) patients by HRM PCR. These patients showed a significantly higher level of percentage of positive-stained cells (% positive cells) and normalized median fluorescence intensity (MFI) for mutant NPM1 by flow cytometry than the negative mutation group. CONCLUSION: Flow cytometric detection of mutant NPM1 offers a possible tool to indicate NPM1 mutational status.

Impact of thrombophilic genes mutations on thrombosis risk in Egyptian nonmetastatic cancer patients.

Venous thromboembolism (VTE) is a common complication in cancer patients. Several genetic risk factors related to thrombophilia are known; however, their contributions to thrombotic tendency in cancer patients have conflicting results. We aimed to determine the prevalence of factor V Leiden (FVL), prothrombin (PTH) G20210A and methylene tetrahydrofolate reductase (MTHFR) C677T gene polymorphisms in Egyptian nonmetastatic cancer patients and their influence on thrombosis risk in those patients. Factor V Leiden, PTH G20210A and MTHFR C677T polymorphisms were detected in 40 cancer patients with VTE (group 1) and 40 cancer patients with no evidence of VTE (group 2) by PCR-based DNA analysis. Factor V and MTHFR mutations were higher in group 1 than in group 2 (factor V heterozygous mutation: 20 vs. 7.5%, homozygous mutation: 10 vs. 2.5%; MTHFR heterozygous mutation: 40 vs. 25%, homozygous mutation 5 vs. 0%, respectively) (P = 0.03). Mortality rate was higher in group 1 (75%) than in group 2 (25%; P < 0.001). No difference was found between those groups regarding PTH mutation (P = 1). Mortality rate was higher in the presence of homozygous and heterozygous factor V mutation (100 and 82%, respectively) compared to the wild type (41%) (P = 0.0006). Having any of the three studied gene mutations worsened the overall survival (P = 0.0003). Cox regression proved that both thrombosis and presence of factor V mutation are independent factors affecting survival in cancer patients (P < 0.001 and P = 0.01, respectively). In conclusion, there is an association between factor V and MTHFR mutations and risk of VTE in Egyptian cancer patients. Thrombosis and presence of factor V mutation are independent factors that influence survival in those patients.