Study the association of microRNA polymorphisms (miR-146a, miR-4513) with the risk of coronary heart diseases in Egyptian population.

Coronary heart disease (CHD) is the most prevalent cause of cardiovascular mortality in the world. It is well established that microRNAs (miRNAs) and their variants have an essential role in regulating the development of cardiovascular physiology, thus impacting the pathophysiology of heart diseases. This study was designed to determine the possible association of miRNA polymorphisms (miRNA-146a rs2910164C/G and miR-4513 rs2168518G/A) with susceptibility to CHD in Egyptian patients and their correlation with different biochemical parameters. The study comprised 300 participants, including 200 unrelated patients with CHD and 100 healthy controls. Anthropometric and blood biochemical parameters were measured as well genetic analysis for rs2910164C/G and rs2168518G/A polymorphisms were performed for all subjects using TaqMan real-time PCR assay. Our results revealed that the biomedical parameters have a significant correlation between CHD patients and healthy controls with a p < 0.05. Analyses of genotype distribution for (rs2910164 and rs2168518) revealed a significant association with CHD [odd ratio = 4.54, confidence interval (CI 95%) = (2.41-8.53)] and [odd ratio = 0.88, (CI 95%) = (0.83-0.92)], respectively. Furthermore, a statistically significant difference was detected between lipid profile levels and both rs2910164 and rs2168518 polymorphisms. The present study's findings indicated that the selected polymorphisms, miR-146a rs2910164 and miR-4513 rs2168518 could represent a useful biomarker for susceptibility to CHD in the Egyptian population. These genetic characteristics and personal habits and environmental factors may contribute to the development of CHD.

The effect of insulin-loaded gold and carboxymethyl chitosan nanoparticles on gene expression of glucokinase and pyruvate kinase in rats with diabetes type 1.

The goal of this study was to see how effective subcutaneous (SC) insulin is and two different types of oral insulin-loaded nanoparticles (INS) including carboxymethyl chitosan nanoparticles (CMCNPs) and gold nanoparticles (AuNPs) separately and compare their effects on glucokinase, pyruvate kinase gene expressions, and other parameters in diabetes type one male Wistar rats. Seven groups of ten male Wistar rats for each group were formed at random including four control groups (n = 10) and three treatment groups (n = 10). The control groups consisted of four control groups (10 rats for each) and three treatment groups (10 rats for each). Normal control rats were not given any treatment, as were diabetic rats that were not given any treatment, and diabetic rats that were given oral nanoparticles (CMCNPs and AuNPs). Diabetic rats were given subcutaneous insulin, oral insulin-loaded carboxymethyl chitosan nanoparticles (INS-CMCNPs), and oral insulin-loaded gold nanoparticles (INS-AuNPs). The rats were treated for the final 3 weeks of the experiment, which lasted 4 weeks. CMCNPs and AuNPs presented a promising effect on pyruvate kinase and Glucokinase gene expressions compared to subcutaneous insulin. We also discovered that conjugating insulin to CMCNPs and AuNPs protects them from the insulin-degrading enzyme, which offers managed bioavailability. Furthermore, we investigated the effects of CMCNPs and AuNPs on several parameters and discovered that both have a significant effect in vivo, which enables glucose level regulation, and improves patient organ activity for better glucose consumption. PRACTICAL APPLICATIONS: In this paper, we discussed the effect of oral INS-CMCNPs and INS-AuNPs, and compared their effects on Glucokinase and pyruvate kinase gene expressions and other biochemical parameters in diabetes type one male Wistar rats. On the other hand, we investigated the impact of oral INS and subcutaneous insulin separately on the same parameters and their effect on the histology of the liver and pancreas of diabetic rats. According to our research, as we discussed the different mechanisms of INS-CMCNPs and INS-AuNPs, they presented a promising effect compared to SC insulin. They can be used to keep oral insulin safe from the environment of the gastrointestinal system to overcome all the barriers, improve the therapeutic, and clinical outcomes of insulin by maintaining its desired concentration inside the body, ending the panic of the patient from receiving insulin by the SC injection by increasing his satisfaction with receiving accurate oral insulin doses.

Primary hyperoxaluria type 1 in children: Clinical classification, renal replacement therapy, and outcome in a single centre experience.

Primary hyperoxaluria type 1 (PH1) is a rare disease that is challenged by the overproduced oxalate and commonly presented with radiopaque renal stones or obstructive uropathy. This study aimed to report clinical presentations, renal replacement therapy (RRT), and outcome of PH1 in end stage kidney disease (ESKD) children. This is an observational cohort study. Data of 22 patients with ESKD due to PH1 were analyzed at Pediatric Nephrology Unit, Faculty of Medicine Cairo University. Infantile onset patients (n = 10) had worst renal outcome (80% with ESRD at presentation, p = 0.019) and worse patient outcome (mortality 40%, p = 0.016) than juvenile (n = 9) and late onset (PH1 n = 3) patients. RRT modalities include peritoneal dialysis (PD) in 7 (31.8%), hemodialysis (HD) in 11 (50%), and combined liver kidney transplantation (CLKT) in 4 (18.2%) patients. Infectious complications were encountered in 42.8% of PD patients. Better HD adequacy was observed with frequent HD (n = 6) and/or HD via arteriovenous fistula (AVF) than with infrequent dialysis (n = 5) and/or via central venous line (CVL) (p = 0.0001 and 0.0047, respectively). Morbidity and mortality (infection related) rates of the whole cohort were 63.6% and 31.8%, respectively. Clinical presentation of PH1 varies according to the age of onset (infantile onset being the most aggressive form). Aggressive HD (better through AVF) is needed to achieve acceptable HD adequacy, PD was challenged by infection. Infection found to be the main cause of mortality even after successful CLKT.

Association of a novel Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)-3928C/T and GM-CSF(3606T/C) Promoter gene polymorphisms with the pathogenesis and severity of acne vulgaris: A case-controlled study.

BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is believed to play an important role in the development of acne vulgaris. AIM OF THE WORK: To investigate the presence of GM-CSF 3928C/T and GM-CSF 3606 T/C promoter gene polymorphisms in Egyptian acne patients. METHODS: To examine whether GM-CSF single nucleotide polymorphisms (SNPs) are associated with susceptibility to acne vulgaris (AV), we investigated the genotype and allele frequencies of the SNP 3928C/T and 3606T/C of the GM-CSF gene in 100 Egyptian acne patients (29 with mild acne, 38 with moderate acne, and 33 with severe acne) and 100 controls, using a PCR restriction fragment length polymorphism (RFLP) method. RESULTS: There was a highly significant difference in genotype and allele frequencies of the 3928C/T group between patients with acne vulgaris and controls for the SNP site. Regarding the 3606 T/C subgroup only a marginal significant difference was found between cases and controls in TC pattern (p = 0.039); with the TC genotype appearing more in cases (53% of patients) than controls (35% of healthy controls). CONCLUSION: We report a novel GM-CSF 3928C/T promoter gene polymorphism contributing to the pathogenesis of acne in Egyptian population.

Cyclooxygenase-2 Gene Polymorphisms -765G>C and -1195A>G and Mycosis Fungoides Risk.

BACKGROUND: Cyclooxygenase-2 (COX-2) is an inducible modulator of inflammation that acts through increasing prostaglandin levels and has been described as a major mediator linking inflammation to cancer. Previous studies supported that COX-2-765G>C and -1195A>G polymorphisms were associated with increased risk of several solid tissue cancers as well as some hematological malignancies. OBJECTIVE: The aim of the study was to elucidate the association between functional COX-2 genotypes (-765G>C and -1195A>G) polymorphisms and the risk of developing mycosis fungoides (MF). METHODS: This was a hospital-based, case-control study of 70 MF patients and 100 MF-free controls. We genotyped COX-2 -1195A>G, -765G>C, and -8473T>C polymorphisms by using the PCR-restriction fragment length polymorphism method. RESULTS: The AA genotype in the COX-2 -1195A>G gene polymorphism and the GC genotype in the COX-2 -765G>C gene were significantly more frequent among MF patients compared to controls (p< 0.001 and p = 0.002, respectively). CONCLUSION: The -results indicate a possible role of COX-2 genes in the pathogenesis of MF. These novel findings may allow for notable future advances, as it will enable the identification of the -individuals most susceptible to MF.

JAK1 rs310241 and JAK3 rs3008 Genotypes May Increase Susceptibility to Psoriasis: A Case Control Study.

BACKGROUND: Janus kinases (JAKs) are a family of non-receptor protein tyrosine kinases that are expressed in a variety of tissues. Several JAK-controlled cytokine receptor pathways are incriminated in the initiation and progression of psoriasis. Genetic polymorphisms influencing JAK expression would be anticipated to have a great impact on disease activity. OBJECTIVE: The aim of the study was to evaluate the association between JAK1 rs310241 and JAK3 rs3008 polymorphisms and the risk of developing psoriasis. METHODS: Blood samples of 150 patients and 120 controls were screened for nucleotide polymorphisms in JAK1 rs310241 and JAK3 rs3008 genes by using polymerase chain reaction (PCR)-restriction fragment length polymorphism technique. RESULTS: The GG genotype of the JAK1 rs310241 and JAK3 rs3008 genes was significantly associated with an increase in psoriasis risk (p = 0.000, OR = 7.7, 95% CI = 2.8-21.5; p = 0.003, OR = 3.3, 95% CI = 1.5-6.9, respectively). The G allele of both genes was also associated with psoriasis susceptibility (p = 0.000, OR = 2.0, 95% CI = 1.4-2.8; p = 0.002, OR = 1.7, 95% CI = 1.2-2.4, respectively). CONCLUSION: The results indicate a possible association between JAK1 rs310241 and JAK3 rs3008 gene polymorphisms and susceptibility to psoriasis. These findings validate the importance of these molecules in psoriasis and may enable the identification of the individuals most susceptible to the disease.

Osteoblast-Based Therapy-A New Approach for Bone Repair in Osteoporosis: Pre-Clinical Setting.

BACKGROUND: Osteoporosis is a metabolic bone disease characterized by low bone density resulting in increased fracture susceptibility. This research was constructed to uncover the potential therapeutic application of osteoblasts transplantation, generated upon culturing male rat bone marrow-derived mesenchymal stem cells (BM-MSCs) in osteogenic medium (OM), OM containing gold (Au-NPs) or gold/hydroxyapatite (Au/HA-NPs) nanoparticles, in ovariectomized rats to counteract osteoporosis. METHODS: Forty rats were randomized into: (1) negative control, (2) osteoporotic rats, whereas groups (3), (4) and (5) constituted osteoporotic rats treated with osteoblasts yielded from culturing BM-MSCs in OM, OM plus Au-NPs or Au/HA-NPs, respectively. After 3 months, osterix (OSX), bone alkaline phosphatase (BALP), sclerostin (SOST) and bone sialoprotein (BSP) serum levels were assessed. In addition, gene expression levels of cathepsin K, receptor activator of nuclear factor-κb ligand (RANKL), osteoprotegerin (OPG) and RANKL/OPG ratio were evaluated using real-time PCR. Moreover, histological investigation of femur bone tissues in different groups was performed. The homing of implanted osteoblasts to the osteoporotic femur bone of rats was documented by Sex determining region Y gene detection in bone tissue. RESULTS: Our results indicated that osteoblasts infusion significantly blunted serum BALP, BSP and SOST levels, while significantly elevated OSX level. Also, they brought about significant down-regulation in gene expression levels of cathepsin K, RANKL and RANKL/OPG ratio versus untreated osteoporotic rats. Additionally, osteoblasts nidation could restore bone histoarchitecture. CONCLUSION: These findings offer scientific evidence that transplanting osteoblasts in osteoporotic rats regains the homeostasis of the bone remodeling cycle, thus providing a promising treatment strategy for primary osteoporosis.

A study of the association of glutathione S-transferase M1/T1 polymorphisms with susceptibility to vitiligo in Egyptian patients.

BACKGROUND: The association of glutathione S-transferases M1/T1 (GSTM1/T1) null polymorphisms with vitiligo was proposed in several studies including two Egyptian studies with contradictory results. OBJECTIVE: The aim here was to assess the association between GSTM1/T1 null polymorphisms and the susceptibility to vitiligo in a larger sample of Egyptian patients with generalized vitiligo. METHODS: This study included 122 vitiligo patients and 200 healthy controls that were age, and gender matched. Assessment of GSTM1/T1 gene polymorphisms was done using a multiplex polymerase chain reaction (PCR). RESULTS: Increased odds of generalized vitiligo was observed with the null genotypes of GSTM1 and GSTT1 polymorphisms (P<0.05). Controls with GSTM1 null/GSTT1+ heterozygosis presented with a 2.97 odds protection from having generalized vitiligo (OR=2.97, 95%CI=1.1-7.7) (P=0.02) compared with patients. STUDY LIMITATIONS: Small sample size of patients. CONCLUSIONS: This study showed a significant trend towards an association with the combination of the GSTM1/GSTT1 double null polymorphism and generalized vitiligo. Individuals with GSTM1 null/GSTT1+ heterozygosis have a 2.97 odds protection from having generalized vitiligo compared with patients. It was is the first time, to our knowledge, that such an association has been reported.

A study of the association of glutathione S-transferase M1/T1 polymorphisms with susceptibility to vitiligo in Egyptian patients

Abstract: Background: The association of glutathione S-transferases M1/T1 (GSTM1/T1) null polymorphisms with vitiligo was proposed in several studies including two Egyptian studies with contradictory results. Objective: The aim here was to assess the association between GSTM1/T1 null polymorphisms and the susceptibility to vitiligo in a larger sample of Egyptian patients with generalized vitiligo. Methods: This study included 122 vitiligo patients and 200 healthy controls that were age, and gender matched. Assessment of GSTM1/T1 gene polymorphisms was done using a multiplex polymerase chain reaction (PCR). Results: Increased odds of generalized vitiligo was observed with the null genotypes of GSTM1 and GSTT1 polymorphisms (P<0.05). Controls with GSTM1 null/GSTT1+ heterozygosis presented with a 2.97 odds protection from having generalized vitiligo (OR=2.97, 95%CI=1.1-7.7) (P=0.02) compared with patients. Study Limitations: Small sample size of patients. Conclusions: This study showed a significant trend towards an association with the combination of the GSTM1/GSTT1 double null polymorphism and generalized vitiligo. Individuals with GSTM1 null/GSTT1+ heterozygosis have a 2.97 odds protection from having generalized vitiligo compared with patients. It was is the first time, to our knowledge, that such an association has been reported.

Study of the relation between two common cyclooxygenase 2 gene polymorphisms with risk of developing and subtypes of vitiligo in Egyptian patients.

BACKGROUND/PURPOSE: Genetic factors play an important role in the pathogenesis of vitiligo. Cyclooxygenase 2 (COX2) gene induced by ultraviolet radiation controls the synthesis of prostaglandins, which are are found to be beneficial in treating vitiligo. COX2 gene polymorphism has been previously evaluated in Chinese population. We aimed to study the relation between two common COX2 gene polymorphisms with vitiligo and its subtypes amongEgyptian patients. PATIENTS AND METHODS: This study included 200 participants (100 vitiligo patients and 100 healthy controls). COX2-765G/C and -1195A/G gene polymorphism was studied by restriction fragment length polymorphism polymerase chain reaction analysis and the results were compared between the two groups and among different subtypes of vitiligo. RESULTS: Frequency of COX2-1195 AA, AG, GG genotypes showed no significant association among patients with vitiligo (P = 0.626, 0.321, 0.08, respectively); those with generalized vitiligo (P = 0.739, 0.291, 0.101, respectively) and those with segmental vitiligo (P = 0.410, 1.00, 0.676, respectively) compared to the control group. Regarding COX2-765G/C genotypes, GG genotype was more frequent among patients with vitiligo [84 (84%)] compared to controls [63 (63%)] (P = 0.001). GC genotype was significantly less frequent [15 (15%)] among patients compared to controls [32 (32%)] (P = 0.005). Generalized and segmental types of vitiligo also showed no significant difference in the frequency of COX2-765G/C genotypes compared with controls. LIMITATIONS: Being a pilot study, a relatively small number of participants were included. CONCLUSION: COX2-1195A/G gene polymorphism is not associated with the risk of developing vitiligo or with vitiligo subtypes. COX2-765 GG genotype is associated with vitiligo, especially of the generalized type.

Insights for hepatitis C virus related hepatocellular carcinoma genetic biomarkers: Early diagnosis and therapeutic intervention.

The current review explores the role of emerging molecular contributing factors in liver carcinogenesis on top of hepatitis C virus (HCV). Here we will try to discuss the role genetic and epigenetic factors in pathogenesis of hepatocellular carcinoma. Understanding the role of these factors will help in discovering the mystery of liver carcinogenesis on top of chronic HCV infection. Moreover, use of the studied molecular factors will provide the hepatologists with tailored diagnostic promising biomarkers and flatten the way for establishment of emerging molecular treatment based on exploring the molecular subscription of this aggressive liver cancer.

The role of microRNA-31 and microRNA-21 as regulatory biomarkers in the activation of T lymphocytes of Egyptian lupus patients.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by familial aggregation and genetic predisposition. MicroRNAs (MiRNAs) serve as critical biomarkers in lupus patients because of their aberrant expression in different SLE stages. The study aimed to investigate the correlation of miR-31 and miR-21 with IL-2 in SLE patients as regulatory biomarkers in the activation of T lymphocytes of Egyptian lupus patients. Quantitative RT-PCR is carried out to estimate the expressions of miR-31 and miR-21, and IL-2 levels were determined using ELISA in plasma of 40 patients with SLE, 20 of their first-degree relatives and 20 healthy controls. The study also determined the systemic lupus erythematosus disease activity index (SLEDAI) score and proteinuria in SLE patients. The results revealed that miR-31 was lower expressed, while miR-21 was high expressed in SLE patients compared to their first-degree relatives and controls. MiR-31 was negatively correlated with SLEDAI and proteinuria in lupus patients, while miR-21 showed positive correlation with them. Also we found that there is a significant positive correlation between miR-31 and IL-2 in SLE patients, while miR-21 was negatively correlated with IL-2 level in patients. In conclusion, the study disclosed a significant association between miR-31 and miR-21 expression with IL-2 level in SLE patients. The regulatory biomarkers of miR-31 and miR-21 might have an impact on regulating IL-2 pathway expression and in turn on the activation of T lymphocytes in SLE.

Is There a Link between Human Herpesvirus Infection and Toll-like Receptors in the Pathogenesis of Pityriasis Rosea? A Case-control Study.

Human herpesvirus (HHV) 6 and 7 are involved in the pathogenesis of pityriasis rosea (PR). Our aim was to evaluate the role of the innate immune response in PR through the detection of Toll-like receptors (TLR) 2, 3, 4, 7, 8, and 9 expression in the skin of affected patients and to detect the possibility of being induced by HHV-6 and/or HHV-7 viral coexistence in these patients. Twenty-four patients with PR and 24 healthy controls were included in this case-control study. Biopsy was obtained from the PR lesion and from the healthy skin of controls for detection of HHV-6 and 7 as well as TLRs 2, 3, 4, 7, 8, and 9 gene expression using real-time polymerase chain reaction (PCR). Significantly elevated expression of all studied TLRs and significantly higher viral load of HHV-6 and 7 in PR cases were detected. A significant higher expression of TLR2 and 4 in HHV-7 positive cases and a significant positive correlation between TLR9 and HHV-7 viral load were documented. HHV6 and 7 may also be involved in the pathogenesis of PR via TLR pathways.

Polymorphisms at IL28B gene as predictors of viral relapse in genotype 4 Egyptian hepatitis C patients.

Chronic HCV is one of the commonest causes of chronic liver disease worldwide with about 15% of population infected in Egypt. Certain single nucleotide polymorphisms (SNPs) lying near the IL28B gene were found to affect the spontaneous clearance as well as treatment outcome of HCV. To examine the association between different IL28B variants and the relapse of HCV infection after combined therapy with ribavirin and pegylated interferon (pegIFN). Hundered HCV genotype four patients received 1.5 mg/kg/week peginterferon alfa-2b plus 800-1400 mg/d ribavirin (weight-adjusted) for 48 weeks. IL28B polymorphisms (rs12980275, rs12979860, and 1 rs8099917) were studied in responders and relapsers at week 72. Out of 69 patients receiving treatment, 13 (18.8%) were relapsers. By stratifying patients on the basis of the IL-28/60 genotype (CC vs. CT/TT), CC patients showed lower relapse rates (2.3%) compared with CT/TT patients (46.2%) (P < 0.001). On the basis of the IL-28/75 genotype (GG vs. GA/AA), the GG patients achieved higher relapse rates (62.5%) compared with GA/AA patients (13.1%) (P = 0.004). Moreover, no statistical significant difference was observed between the TT patients compared with GG/GT patients on the basis of the IL-28/17 genotype. SNPs at IL-28/60 and IL-28/75 are possible predictors of relapse in patients receiving dual treatment.

Evaluating the association of APOA2 polymorphism with insulin resistance in adolescents.

BACKGROUND: 265T>C SNP in the APOA-II gene promoter may be associated with obesity risk and insulin resistance (IR). This study aims to analyze the association between the APOA2 - 265T>C SNP and risk for obesity and IR in adolescents. MATERIAL AND METHODS: The study was conducted on 500 adolescents. They were 240 obese and 260 non-obese individuals, aged 16-21 years old. Their mean age was 18.25 ± 2.54 years. Variables examined body weight, height, waist circumference (WC), systolic and diastolic blood pressure (BP), body fat percentage (BF%), and abdominal visceral fat layer. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was used as a biomarker for IR. BF% was assessed by body composition analyzer and abdominal visceral fat thickness was determined by ultrasonography. The APOA2 - 265T>C polymorphism genotype was analyzed by PCR amplification of a 273-bp fragment. RESULTS: Genotype frequencies were in Hardy-Weinberg equilibrium. The frequency of the mutant C allele was significantly higher in obese cases than non-obese cases. After multivariate adjustment, waist, BF%, visceral adipose layer and HOMA-IR were significantly higher in homozygous allele CC carriers than TT + TC carriers. Homozygous individuals for the CC allele had statistically higher values of energy intake, total fat (g/day) and saturated fat (SATFAT) than carriers of the T allele. CONCLUSIONS: Homozygous individuals for the C allele had higher obesity risk than carriers of the T allele and had elevated levels of visceral adipose tissue. Moreover, the present study shows that the CC polymorphism is associated with the development of IR [OR 1.89 (1.35-2.91), P = .012] and remains significant after adjusting for gender, age and body mass index.

APOA2 Polymorphism in Relation to Obesity and Lipid Metabolism.

Objectives. This study aims to analysis the relationship between c.-492T>C polymorphism in APOA2 gene and the risk for obesity in a sample of Egyptian adolescents and investigates its effect on body fat distribution and lipid metabolism. Material and Methods. A descriptive, cross-sectional study was conducted on 303 adolescents. They were 196 obese and 107 nonobese, aged 16-19 years old. Variables examined included body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), systolic and diastolic blood pressure (BP), body fat percentage (BF%), abdominal visceral fat layer, and dietary intake. Abdominal visceral fat thickness was determined by ultrasonography. The polymorphism in the APOA2 c.-492T>C was analyzed by PCR amplification. Results. Genotype frequencies were in Hardy-Weinberg equilibrium. The frequency of the mutant C allele was significantly higher in obese cases compared to nonobese. After multivariate adjustment, waist, BF% and visceral adipose layer, food consumption, and HDL-C were significantly higher in homozygous allele CC carriers than TT+TC carriers. Conclusions. Homozygous individuals for the C allele had higher obesity risk than carriers of the T allele and had elevated levels of visceral adipose tissue and serum HDL-C. Moreover, the study shows association between the APOA2 c.-492T>C polymorphism and food consumption.