Association of MNS16A VNTR and hTERT rs2736098: G>A polymorphisms with susceptibility to diffuse large B-cell lymphoma.

PURPOSE: Genetic studies of diffuse large B-cell lymphoma (DLBCL) may serve to clarify disease pathogenesis and mark at-risk populations. Evidence of long telomeres and high telomerase activity have been demonstrated in DLBCL. We aimed to examine human telomerase gene ( hTERT) MNS16A variable number of tandem repeats and hTERT rs2736098: G>A polymorphisms in relation to DLBCL susceptibility. METHODS: In a case control study, 71 patients with DLBCL and 156 controls were genotyped for MNS16A using polymerase chain reaction and hTERT rs2736098: G>A using polymerase chain reaction restriction fragment length polymorphism. RESULTS: In both codominant and recessive models, there was a significant difference in the distribution of MNS16A genotypes between patients with DLBCL and controls (p = 0.047 and p = 0.018, respectively). In both models, carriers of S/S genotype were at higher risk to develop DLBCL (odds ratio [OR] 2.51, 95% confidence interval [CI] 1.19-5.29 and OR 2.19, 95% CI 1.15-4.17, respectively). In the log-additive model, each copy of S allele significantly increased DLBCL risk in an additive form (p = 0.018, OR 1.57, 95% CI 1.08-2.29). The frequency distribution of MNS16A S alleles was significantly higher in patients than controls (p = 0.012). Carriers of S alleles were at higher risk to develop DLBCL than carriers of L alleles (OR 1.67, 95% CI 1.12-2.49). hTERT rs2736098: G>A genotype distribution did not differ significantly between patients with DLBCL and controls. CONCLUSIONS: MNS16A genetic variations are associated with DLBCL susceptibility.

Increased expression of brother of the regulator of imprinted sites in peripheral blood neutrophils is associated with both benign and malignant breast lesions.

BACKGROUND: BORIS, a paralog of the multifunctional CCCTC-binding factor (CTCF) gene is restricted to testis and normally not present in females. It is aberrantly activated in various human cancers including cancer breast. Using immunohistochemistry, western blot and/or RT-PCR, significantly higher levels of BORIS expression were reported in the neutrophils of cancer breast patients. We hypothesized that Flow Cytometry might be a better technique for objective quantitative evaluation of BORIS in neutrophils and we wanted to investigate if BORIS would discriminate between benign and malignant breast lesions. METHODS: The study included 85 females; 52 breast cancer, 13 benign breast lesions and 20 age-matched healthy controls. BORIS expression in the neutrophils was detected by Flow Cytometry. RESULTS: High level of BORIS was detected in all malignant (64.4 ± 16.6%) and benign cases (67 ± 12.3), mean florescent intensity ratio (MFIR) of 7.2 ± 4.1 and 7 ± 3.5, median 5.8 and 6.6%; and staining index (SI) 8.3 ± 3.9 and 8.2 ± 3.4, median 7.6 and 7.9 respectively vs.13.4 ± 11.5% MFI 1.8 ± 0.7, median1.6 and SI 2.6 ± 0.69, median 2.5 for the control. BORIS level was comparable in the malignant and benign group (P = 0.934) and significantly higher than control (P = 0.0001). There was no correlation between neutrophil BORIS expression and ER/PR status, HER-2/neu expression or tumor stage or size. CONCLUSIONS: Increased BORIS expression in peripheral blood neutrophils is associated with both benign and malignant breast lesions; apparently, increased proliferation of breast tissue is the determining factor. This excludes BORIS as a tumor marker but it does not jeopardize its value as a potential therapeutic target. © 2016 International Clinical Cytometry Society.

Elevated serum adiponectin is related to elevated serum ferritin and interleukin-6 in ß-thalassaemia major children.

BACKGROUND: There is evidence that iron affects lipid metabolism and adipocyte biology. Given the effects of iron on adiponectin, the role of iron in lipid oxidation, and the potential additive effects of oxidative stress from excess iron and lipid metabolism. We aimed to investigate serum adiponectin in relation to clinical and laboratory parameters including the inflammation markers [C-reacitve protein (CRP) and interleukin-6 (IL-6)] in ß-thalassaemia major children. METHODS: We investigated 58 ß-thalassaemia major children under scheduled blood transfusion and 30 controls. Routine clinical evaluation, laboratory investigations including serum ferritin as well as CRP measured by immunoturbidimetry, IL-6 and serum adiponectin measured by ELISA are performed. RESULTS: CRP, IL-6 and serum adiponectin levels were higher in patients than controls (p<0.001, p=0.04 and p<0.001, respectively). Patients received desferoxamine showed significantly lower levels of adiponectin than those did not receive it (mean±SD=4.50±3.37 vs. 9.96±9.68, p=0.006). Serum adiponectin was significantly negatively correlated with hemoglobin (Hb) concentration (r=-0.36, p=0.005). It was significantly positively correlated with platelets count, serum ferritin, CRP and IL-6 (r=0.27, r=0.26, r=0.30, r=0.35, respectively and p=0.04, p=0.04, p=0.01, p=0.008, respectively). Serum ferritin and IL-6 were the significant predictors of serum adiponectin level (p<0.001 and p=0.003, respectively). CONCLUSIONS: Serum adiponectin was increased in ß-thalassaemia major as were pro-inflammatory markers (CRP and IL-6). Its level is directly associated with ferritin and IL-6 levels.

Association Between Plasminogen Activator Inhibitor-1-675 4G/5G Insertion/Deletion Polymorphism and Chronic Obstructive Pulmonary Disease.

Molecular pathology of chronic obstructive pulmonary disease (COPD) is still being investigated to discover relationships with disease pathogenesis. Evidence of plasminogen activator inhibitor-1 (PAI-1) overexpression in the sputum and the blood of COPD patients is growing. We aimed to investigate the potential relation between PAI-1 promoter 4G/5G insertion/deletion polymorphism and COPD development. In a case-control study, we genotyped 117 COPD patients and 160 control subjects for PAI-1 promoter 4G/5G polymorphism by an allele-specific polymerase chain reaction analysis. All subjects were male smokers. In the co-dominant model, there was a significant difference in the distribution of 5G/5G, 4G/5G and 4G/4G genotypes between COPD patients and controls (p = 0.002). In the recessive model, carriers of 4G/4G genotype were significantly higher in COPD patients than controls (p = 0.01). Carriers of 4G/4G genotype were at higher risk to develop COPD than those carrying 5G/5G or 4G/5G genotypes (crude odds ratio (OR) = 2.10, 95% confidence interval (CI) = 1.19-3.73, adjusted OR = 2.5, 95% CI = 1.22-3.99). In conclusion, PAI-1 4G/5G genetic variations are associated with COPD development in males.

sTREM-1 in patients with chronic kidney disease on hemodialysis.

The triggering receptor expressed on myeloid cells-1 (TREM-1) is a member of the immunoglobulin superfamily. TREM-1 has been implicated as an amplifier of inflammation. Soluble TREM-1 (sTREM-1) was investigated in different clinical conditions, but not in hemodialysis (HD) patients. We aimed to investigate sTREM-1 as a marker of inflammation in HD patients. We investigated 40 CKD patients undergoing chronic HD treatment and 15 controls. Routine laboratory investigations in addition to CRP measured by immunoturbidimetry, TNF- α, and sTREM-1 measured by ELISA were assayed in post-hemodialysis patients' blood samples and in controls' blood samples. CRP, TNF-α, and sTREM-1 levels were significantly higher in HD patients than in controls (p < 0.001 for all). sTREM-1 was positively correlated with CRP and TNF-α (r = +0.50, p < 0.001 and r = +0.53, p < 0.001 respectively). It was negatively correlated with hemoglobin concentration (r = -0.69, p < 0.001). Hemoglobin concentration was the significant predictor of sTREM-1 level (p < 0.001). In conclusion, sTREM-1 level is significantly increased in HD patients as are other pro-inflammatory markers.

Peripheral blood mammaglobin gene expression for diagnosis and prediction of metastasis in breast cancer patients.

AIM: To evaluate the value of peripheral blood mammaglobin (MG) gene expression for diagnosis and prediction of metastasis in breast cancer patients. METHODS: MG expression was detected by nested reverse-transcription polymerase chain reaction in the peripheral blood of 46 females (32 breast cancer, 12 benign breast lesions, 2 no breast abnormalities). In total 28 breast cancer patients were followed up through a period of 34 months for the development of metastasis. RESULTS: MG expression was detected in 16/32 (50%) breast cancer patients but not in patients with benign lesions or healthy participants. Five patients had metastasis at diagnosis. During the 34 months of follow up, five more MG-positive patients showed metastatic lesions and none of the MG negative patients who were followed up developed metastasis. CONCLUSION: The study suggests blood MG expression is a specific molecular marker for detection of occult mammary carcinoma cells of patients with operable breast cancer. It might be of value as a predictor of subsequent metastasis. Large-scale studies and longer follow-up periods are needed.

Apolipoprotein E gene variants as a risk factor for coronary artery disease in type 2 diabetic Egyptian patients.

Patients with diabetes mellitus (DM) have increased mortality and morbidity of cardiovascular diseases compared with non-diabetic patients. The role of apolipoprotain E in lipid metabolism and cholesterol transport is well established. Apolipoprotein E gene (APO E) polymprphism that confers susceptibility to or protection from CAD in patients with type 2 DM may be quite different in different ethnic populations. We aimed to determine the frequencies of allelic variants of APO E in Egyptian population and to examine the relationship between APO E polymorphism and risk of coronary artery disease (CAD) in Egyptian type 2 diabetic patients. The study included 35 diabetic patients with CAD (group 1), 35 diabetic patients without CAD (group II) and 30 control subjects. All were subjected to history taking, clinical examination, and laboratory investigations for lipid profile and APO E genotyping by PCR-RFLP. Results revealed that epsilon3 allele was the commonest among the studied subjects (84%). The frequencies of epsilon2 and epsilon4 alleles were higher in group I (24.3% and 8.6% respectively) than group II and controls. The frequency of E2/E2, E2/E3, and E4/E3 genotypes was significantly higher in group I than group II and controls. Comparing group I vs. controls and group I vs. group II, multivariate analysis demonstrated significantly increased risk for CAD with epsilon4 and epsilon2 alleles vs. E3 (OR=7.02 and 4.97 respectively). In Conclusion, epsilon4 and E2 alleles are associated with higher risk of CAD in type2 DM than epsilon3 allele. Larger scale studies are still needed to either confirm or modify these results.