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Background Type 2 diabetes (T2D) is a complex trait in humans. Several environmental and hereditary factors contribute to the overall pathogenesis of this disease. The association between genes, environment, and T2D was unknown for decades until epigenetics was discovered. Epigenetics affects gene transcription, which, in turn, influences organ function. One of the epigenetic regulatory mechanisms is DNA methylation. This mechanism permits modification of gene function without changes in the DNA sequence. There are several risk factors for type 2 diabetes such as harmful intrauterine environment, obesity, poor physical activity, increasing age, a family history of the disease, and an unhealthy diet. All these factors have been proven to influence the DNA methylation sequence in target tissues for insulin resistance in humans. We aimed to evaluate insulin-like growth factor binding protein-1 (IGFBP1) gene methylation levels in T2D. In all, 100 Egyptian individuals were included in this study: 50 patients with T2D versus 50 healthy controls. Genomic DNA was extracted from peripheral blood and IGFBP1 methylation levels were analyzed using pyrosequencing. Results DNA methylation levels in the IGFBP1 gene at each of the six CpG sites were significantly higher in the T2D patients than in the controls at P values of 0.001, 0.002, 0.010, 0.007, 0.014, and 0.001, respectively. Conclusion According to this study, T2D is due to interactions between genetics, epigenetics, and lifestyle. This study also revealed that DNA methylation levels of the IGFBP-1 gene are higher in T2D patients than in healthy control.

We studied the impact of socioeconomic level on the anti‐SARS‐CoV‐2‐antibodies prevalence in an Egyptian cohort. The low socioeconomic standard group (LSS) included 51 humans, 30 females (F) and 21 males (M). The high socioeconomic standard group (HSS) included 55 subjects, 24 F and 31 M. Of the 30 LSSF, 6 were immunoglobulin M (IgM), 21 immunoglobulin G (IgG), and 6 double positive. Of the 21 LSSM, 5 were IgM, 12 IgG, and 5 double positive. Of the 24 HSSF, 6 were IgM, 11 IgG, and 5 double positive. Of the 31 HSSM, 6 were IgM, 14 IgG, and 4 double positive. Of the 51 LSS humans, 26 were symptomatic (S) and 25 asymptomatic (AS). Of the 26 S, 20 were IgG and 8 IgM/IgG double positive. Of the 25 AS, 13 were IgG and 3 IgM/IgG double positive. Of the 55 HSS humans, 38 were S and 17 AS. Of the 38S, 24 were IgG and 11 IgM positive of whom, 9 were double positive. Of the 17 AS, one was IgG and one IgM positive. The IgM prevalence was higher among the HSS humans. The IgG prevalence was significantly higher among the LSS humans. In the two different socioeconomic standards, the prevalence of either IgM or IgG was higher among F. An inverse correlation was observed between age and the anti‐SARS‐CoV‐2‐antibodies prevalence except for LSSF‐IgG and LSSM‐IgM. In conclusion, socioeconomic standard, gender, and age impact humoral responses to SARS‐CoV‐2 with a clear heterogeneity in individualized responses to the infection in terms of symptoms., Highlights Socioeconomic standard, gender, and age impact humoral responses to SARS‐CoV‐2 with a clear heterogeneity in individualized responses to the infection in terms of symptoms.

Objective: Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) gene is one of the possible genes linking diabetes mellitus (DM) with coronary artery disease (CAD). The aim of this study is to clarify whether PPAR-γ Pro12Ala polymorphism is associated with the development of CAD in type 2 diabetic patients and to evaluate PPAR-γ Pro12Ala polymorphism genetic distribution in type 2 DM (T2DM) Egyptian subjects. Methods: PPAR-γ Pro12Ala polymorphism was determined by Real-Time PCR in serum of 405 subjects classified into 4 groups; T2DM patients (n = 105), T2DM with CAD (n = 100), CAD patients (n = 100) and healthy controls (n = 100). Results: The PPAR-γ Pro12Ala polymorphism was associated significantly with T2DM with CAD (group2) (OR = 3, 95% CI = (1.5–6); p = 0.001). In this study, T2DM with CAD complications carrying the PPAR-γ Pro12Ala polymorphism had higher BMI than those without the PPAR-γ Pro12Ala polymorphism (p

Background: Diabetes mellitus is considered a major public health problem worldwide. Susceptibility to diabetes is influenced by both genetic and environmental determinants. Aims/hypothesis: The aim of the present study was to test for 16 independent single nucleotide polymorphisms (SNPs) in established Type 2 diabetes (T2D) and obesity susceptibility loci by GWAS in a sample of Egyptian patients to find out if there is shared genetic background underlying both disease entities. Methods: Genotyping was performed using OpenArray® protocol on the QuantStudio™ 12K Flex Real-Time PCR System. In the present case control study a custom array was designed to facilitate cost-effective analysis of selected SNPs related to glycolysis, gluconeogenesis, inflammation, insulin signalling, and immune function. Results: Seven gene variants showed significant association with the risk of T2D patients including FCGRA2, STAT4, CELSR2, PPARG, EXT2 rs3740878, GCKR, PTGS1. Factors that significantly affect T2D were obesity (p

Background: We studied JAZF1, ABCC8, KCNJ11and Notch2 gene expression and vitamin D receptor (VDR) polymorphisms (Fok1 and Bsm1) in patients with type 2 diabetes mellitus (T2DM) and tried to find out their association with microvascular complications in these patients. Methods: The study was conducted on 180 patients (93 complicated and 87 noncomplicated) and 150 healthy subjects. Reverse-transcriptase polymerase chain reaction (RT-PCR) was used to assess gene expression and real-time PCR was used to detect VDR genotypes. Serum vitamin D was assessed using Elisa technique. Results: After adjustment for age, sex, body mass index and glycated hemoglobin, altered Notch2 gene expression was found between patients and controls and between complicated and noncomplicated cases ( p = 0.001 and 0.001, respectively) and ABCC8 gene expression showed significant difference between patients and controls only ( p = 0.003), while JAZF1and KCNJ11 expression showed no significant difference between the studied groups ( p = 0.3 and 0.4, respectively). Serum vitamin D level was decreased in patients compared with controls ( p = 0.001), while no difference was detected between complicated and noncomplicated cases ( p = 0.1). Our results revealed no significant difference in VDR Fok1 and Bsm1 genotype distributions ( p = 0.7 and 0.1, respectively) and allele frequencies ( p = 0.4 and 0.1, respectively) between patients and controls. Patients with complications showed increased frequencies of Fok1GG genotype and G allele, while patients without complications showed increased frequencies of AA, then AG Fok1 genotype and A allele ( p = 0.001 and 0.001, respectively). In addition, the frequencies of CC Bsm1 genotype and C allele were significantly higher among patients with complications, while frequencies of TT Bsm1 genotype and T allele were significantly higher among patients without complications ( p = 0.02 and 0.003, respectively). Conclusion: Altered expression of Notch2 and ABCC8 genes may play a role in the pathogenesis of T2DM. Altered expression of Notch2 and VDR polymorphisms may play a role in the development of microvascular complications in diabetic patients. These results may assist in early identification and management of diabetic complications.

Background Neonatal diabetes mellitus (NDM) is a monogenic form of diabetes mellitus. Until now, patients in developing countries who had this condition had been misdiagnosed as having type 1 diabetes mellitus and accordingly directed to erroneous, ineffective, and costly therapeutic regimens. Objective To detect Egyptian patients who harbor pathological variant in the KCNJ11 gene, so that their treatment regimen can be modified as needed to increase its effectiveness. Methods We sequenced KCNJ11 in 17 ethnic Egyptian probands diagnosed with diabetes mellitus before age 2 years. Results A preliminary case individual harboring a KCNJ11 pathological variant (p.R201H) was identified. The patient was successfully shifted from insulin therapy to sulfonylurea. Four previously identified benign variants, namely, E23K, I337V, L270V, and A190A, were detected in this patient. Conclusion Implementing the findings of this molecular analysis could have a major clinical and nationwide economic impact on world health, especially in developing countries.

Introduction Fc gamma receptor (FcγR) IIa is considered the most widely distributed of the three classes of Fc receptors, and it expresses an allelic polymorphism. This type of polymorphism may modify the immune response and may be an important factor for some diseases. The aim of the study reported herein was to evaluate the association between the FcγRIIa polymorphism and susceptibility to both end-stage renal disease (ESRD) and acute kidney graft rejection (AR) in children who have undergone renal transplantation. Material and methods The study evaluated 70 children who had undergone transplantation and 60 healthy subjects. AR was observed in 25 children. Results FcγRIIa genotypes and alleles were significantly different between transplantation patients and the control group. The assessment for FcγR of the groups in which AR was present showed that there was only a risk of having an acute rejection in homozygous genotype RR. Conclusions FcγRIIa RR genotype and allele frequency was increased in paediatric renal transplant recipients. The present findings showed that FcγRIIa genotype may be related to ESRD disease susceptibility, and FcγRIIa polymorphisms seemed to affect AR.

BACKGROUND: Mild cognitive impairment (MCI) is a stage between the expected cognitive decline of normal ageing and the serious decline of dementia. AIM: To identify risk factors and role of miRNAs associated with mild cognitive impairment (MCI) among employees. SUBJECTS AND METHOD: A cross-sectional study was carried out on 186 employees aged between 40 and 65 years. Cognitive function was evaluated using ACEIII, MoCA, and Quick cognitive tests. Medical history and lifestyle were assessed. Family 132 & 134 miRNA expressions were assessed by real-time PCR. RESULTS: MCI was detected among 14 / 186 (7.5%). miRNA 132 expression was the only significant miRNAs to detect MCI with low sensitivity and specificity (70%). The logistic analysis revealed that higher miRNA132 expressions, low monthly intake of; vegetables, unroasted nuts, low education and higher ALT levels were predicting factors for MCI with AOR 1.1 (1.01-3.3), 1.2 (1.04-1.43), 0.8 (0.8-0.98), 2.7 (1.9-7.4) and 1.6 (1.1-2.3) respectively. CONCLUSION: MiRNAs expression showed low sensitivity and specificity in detecting MCI; only miRNA 132 might be used. Several modifiable factors seem to reduce the risk of MCI.

Background An essential milestone in pediatric transplantation is to find noninvasive biomarkers to monitor acute rejection (AR). In this retrospective (Case-control) study, we examined the role of Fas − 670A/G and Fas Ligand (FasL) − 843C/T gene polymorphisms in allograft nephropathy in pediatric renal transplant recipients. Methods In 47 pediatric kidney transplant recipients and 20 healthy controls, Fas − 670A/G and FasL − 843C/T gene polymorphisms as well as serum soluble Fas Ligand level (sFasL) were measured. Results Serum sFasL levels were significantly higher in transplant recipients children than that in controls (548.25 ± 298.64 pg/ml vs 143.17 ± 44.55 pg/ml, p = 0.0001). There was no significant difference between patients with AR and those without AR in regards to serum sFasL levels (567.70 ± 279.87 pg/ml vs 507.85 ± 342.80 pg/ml, p = 0.56). Fas − 670A/G genotypes or alleles were not significantly different between controls and transplant recipients and among transplant recipients with and without AR. (P > 0.05 for all). FasL − 843C/T genotypes were not different between transplant recipients and controls and among transplant recipients with and without AR (P > 0.05 for all). However, Frequency of C allele in transplant patients was significantly higher than that in the control group (44.68% vs 25%, P = 0.03). FasL − 843C/T alleles were significantly different between patients with and without AR (P = 0.03). The percentages of C allele were higher in children with AR (58.82% vs 36.67%). We found that serum FasL and serum creatinine were variables that were independently associated with AR. Conclusion This study suggests that FasL gene polymorphisms in peripheral blood might be accurate in detecting cellular AR.

Background : End stage renal disease (ESRD) is a common cause of morbidity and mortality among children. Interleukin 4 is a cytokine that might influence the progression of chronic kidney disease (CKD) to end stage renal disease. There are variable number of tandem repeats (VNTRs) in IL4 gene that could play major roles in genetic predisposition to some diseases. Aim of the study: The purpose of this study is to detect the association of allelic variant in intron 3 VNTR-IL4 gene with the end stage renal disease and if these variants could be considered as risk markers for this disease. Subjects and methods : The study was conducted on fifty-five children with CKD and fifty healthy children served as controls. All participants were genotyped for intron 3 VNTR by Polymerase Chain Reaction. Results : The frequency of intron 3 VNTR-IL4 P1P2 + P2P2 genotypes was significantly higher in ESRDchildren than those with P1P1 genotype (88.7% vs. 15.4%, OR 43; 95% CI 13–134, P value < 0.001). Also, the frequency of P2 allele was significantly higher in ESRD-children compared with healthy controls (70.9% vs. 8%, OR 28; 95% CI 12–64, P value < 0.001). Furthermore, a significantly higher frequencies of P1P1 genotype and P1 allele among the control group were demonstrated (84.6% vs. 11.3%, P < 0.001 and 92% vs. 29.1%, P < 0.001, respectively). Conclusion : we concluded that the P2 allele is an allelic variant predisposing to ESRD in children with CKD and it could be considered a risk factor for the development of ESRD. Keywords : VNTR-IL4 ESRD PCR Children Gene polymorphism

Breast cancer remains one of the top threats to women's health. The current lack of tumor markers with desirable sensitivity and specificity is a major obstacle toward the future management of breast cancer. Many studies are directed to reveal the diagnostic and prognostic potentials of circulating miRNAs in breast cancer. In this study, we attempt to evaluate the feasibility and clinical utility of circulating miRNA-21 and let-7 as prognostic biomarkers for breast cancer.Real-time quantitative polymerase chain reaction technique was used. Levels of miRNA-21 and let-7 expression were determined in sera from 125 participants representing 3 different groups. With fold-change analysis, the expression of miRNA-21 and let-7 in the decided groups were assessed.Patients with breast cancer showed significantly higher expression of miRNA-21 compared with controls and other participants with benign breast lesions (P .001). The mean expression levels of serum miRNA-21 was 3.27 ± 2.10-fold in patients with breast cancer. The expression of miRNA let-7 was significantly decreased in patients with breast cancer (2.45 ± 2.20-fold) than the control group and the benign breast lesions group (5.27 ± 3.30-fold and 6.22 ± 4.90-fold, respectively; P .001). Levels of miRNA let-7 expression negatively correlated with development of metastases in patients with breast cancer (P .001).Our study establishes the association between altered levels of miRNA let-7 and metastases risk in patients with breast cancer, implying a role of miRNA let-7 in disease progression and prognosis.

Background Chronic lymphocytic leukemia is a heterogeneous disease characterized by a highly variable clinical course. The majority of cases do not require therapy and show identical survival rate with their chronic lymphocytic leukemia-free counterparts of the same age. However, other patients may suffer from an aggressive course of the disease with early need for therapy and shorter overall survival. Objective The aim of this study was to investigate the expression pattern and prognostic value of the adhesion molecules, CD49d and CD38, in chronic lymphocytic leukemia (CLL) patients. Moreover, we attempted to investigate their correlation with trisomy 12, which could help in the clarification of the distinctive clinical features of the trisomy 12+ CLL subset. Patients and methods Seventy newly diagnosed chronic lymphocytic leukemia patients and 50 age-matched and sex-matched controls were included in this study. Patients were subjected to full history taking, clinical examination and abdominal ultrasonography. Laboratory investigations included complete blood count, cytogenetic analysis for the presence of trisomy 12, and flow cytometric assessment. Results A significant positive correlation was detected between CD49d expression and CD38 expression. CD49d showed positive correlation with poor prognostic parameters that included organomegaly, high count of white blood cells, lymphocyte count and trisomy 12. CD38 showed a significant positive correlation with high white blood cell count, lymphocyte count, and splenomegaly. In addition, trisomy 12+ chronic lymphocytic leukemia patients showed significant higher lymphocyte count and splenomegaly. Conclusion Our data confirm the suggested role of CD38 and CD49d as predictors for poor clinical outcome of CLL patients. Moreover, trisomy 12+ CLL cells exhibit a high CD49d expression that may account for the unique clinical characteristics of this group.