Association between Apo B, LDL-R and PCSK9 gene polymorphisms with coronary artery diseases in Egyptians.

BACKGROUND: Many studies have focused on the significance of lipid regulatory genes in the pathophysiology of Coronary artery disease (CAD). ApoB XbaI (rs693) and EcoRI (rs1042031) single nucleoid polymorphisms (SNPs) were investigated to detect whether they are risk factors for CAD. Till now, this association remains uncertain. SMARCA4 (rs1122608) SNP has directly related to dyslipidemia. Loss of function mutations (LOF) in PCSK9 result in a reduction in LDL cholesterol and are associated with protection from the development of CAD. METHODS: This study was conducted on 54 CAD patients who were admitted at Internal Medicine Specialized Hospital (Cardiology Department) and 47 healthy controls. Peripheral blood samples were taken from both groups. DNA was extracted from EDTA-blood samples, then PCR- RFLP for ApoB XbaI (rs693) and EcoRI (rs1042031), SMARCA4 (rs1122608) and PCSK9 (rs505151) SNPs was done. RESULTS: No statistically significant difference was found between patients and controls as regard EcoRI SNP. XbaI (rs693) X + X + genotype was significantly higher in control group (P = 0.0355). SMARCA4 (TT, GT + TT) genotypes, and T allele (P < 0.001); PCSK9 AG genotype and G allele (P = 0.027 and 0.032 respectively) were more frequent in CAD patients than controls. CONCLUSION: SMARCA4 (rs1122608) and PCSK9 (rs505151) SNPs are significantly accompanying with the risk of CAD development in the Egyptian population. X + X + genotype appeared to have a protective effect against CAD. However, no observed association between EcoRI (rs1042031) and the risk of CAD development was found.

Serum apelin-12 and obesity-related markers in Egyptian children with Down syndrome.

Children with Down syndrome (DS) exhibit higher overweight/obesity rates than their typically developing peers. Apelin-12 is a bioactive adipokine that exerts vital roles in obesity-related cardiometabolic comorbidities. To date, apelin-12 has not been investigated in obese-DS. This study aimed to explore the possible association between serum apelin-12 and obesity-related markers and to evaluate the efficiency of apelin-12 in the prediction of metabolic syndrome (MetS) in obese-DS compared to BMI Z-score matched obese-control. The cross-sectional study included 150 prepubertal children classified into three groups; obese-DS (n = 50), obese-control (n = 50), and normal-weight-control (n = 50). Anthropometric parameters, body adiposity, fasting serum levels of blood glucose (FBG), insulin, lipid profile, and apelin-12 were evaluated. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from FBG and insulin. MetS was defined using Adult Treatment Panel III criteria modified for the pediatric age group. ROC curves were analyzed to evaluate the efficiency of apelin-12 in predicting MetS in obesity groups. Obese-DS exhibited higher body adiposity with marked central fat distribution, atherogenic lipid profile, and higher HOMA-IR compared to obese-control. Apelin-12 was significantly higher in obese-DS and obese-DS with MetS compared to obese-control and obese-control with MetS respectively (p < 0.001). The increase in apelin-12 with higher obesity grades was pronounced in obese-DS. Apelin-12 strongly correlated with body adiposity, several MetS risk factors, and HOMA-IR in obese-DS. Significantly higher AUC for apelin-12 in the diagnosis of MetS among obese-DS than obese-control (AUC = 0.948 vs. AUC = 0.807; p = 0.04). CONCLUSIONS:  The current study supports the crucial role of apelin-12 in obesity-related clinical and biochemical markers and in MetS in obese-DS and obese-control. Serum apelin-12 is a potential diagnostic biomarker for MetS with greater performance in obese-DS than obese-control raising its potential for clinical and therapeutic applications. WHAT IS KNOWN: • Obese-DS children displayed excess body adiposity, Pronounced central fat distribution, atherogenic lipid profile, higher HOMA-IR, and higher prevalence of MetS than obese-control. WHAT IS NEW: • Higher serum apelin-12 was observed in obese-DS and obese-DS with MetS than obese-control and obese-control with MetS respectively. The increase in apelin-12 level with increasing obesity grades was more pronounced in obese-DS. • Apelin-12 strongly correlated with obesity-related markers and MetS components in obese-DS. Apelin-12 performed better as a diagnostic biomarker for MetS in obese-DS than obese-control.

Aquaporin-4 IgG antibodies: predictors of positivity and their relationship with neuropsychiatric disorders and white matter lesions in Juvenile systemic lupus erythematosus.

BACKGROUND: This study aimed to describe the prevalence of the various clinical features and severity of juvenile systemic lupus erythematosus (jSLE) and to assess predictors of AQP4-Ab positivity in jSLE. In addition, we assessed the relationship of AQP4-Abs with neuropsychiatric disorders and white matter lesions in jSLE. METHOD: For 90 patients with jSLE, demographic data, clinical manifestations, and treatments received were recorded, and all of the patients were underwent clinical examinations, including assessments for the neurological manifestations of jSLE and neuropsychiatric disorders; Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score evaluations; laboratory investigations, including serum AQP4-Ab assays; and 1.5 Tesla brain MRI. Echocardiography and renal biopsy were performed for the indicated patients. RESULT: Fifty-six patients (62.2%) tested positive for AQP4-Abs. These patients were more likely to have higher disease activity scores (p < 0.001); discoid lesions (p = 0.039); neurological disorders (p = 0.001), mainly psychosis and seizures (p = 0.009 and p = 0.032, respectively); renal and cardiac involvement (p = 0.004 and p = 0.013, respectively); lower C3 levels (p = 0.006); white matter hyperintensities (p = 0.008); and white matter atrophy (p = 0.03) than patients who were negative for AQP4-Abs. Furthermore, AQP4-Ab-positive patients were more likely to have received cyclophosphamide (p = 0.028), antiepileptic drugs (p = 0.032) and plasma exchange therapy (p = 0.049). CONCLUSION: jSLE patients with higher severity scores, neurological disorders, or white matter lesions could develop antibodies against AQP4. We recommend more studies for systematic screening of AQP4-Ab positivity in jSLE patients to confirm its relationship with neurological disorders.

Peroxisome proliferator-activated receptor γ Pro12 ala polymorphism and risk of cerebral stroke in type 2 diabetes mellitus egyptian patients.

Objectives: This study aimed to analyze the association of the peroxisome proliferator activated receptor gamma (PPARγ) P12A (rs1801282) polymorphism with development of cerebral stroke in patients with type 2 diabetes mellitus. Methods: We included 224 patients with diabetes, they were categorized into116 patients with ischemic stroke (IS) and 108 without IS, in addition to 148 healthy controls in this study. respectively. Anthropometric parameters and laboratory tests were measured. The polymorphism was detected by a PCR-RFLP method. Results: A12 allele and A12 containing genotypes show significant higher percentage in patients with diabetes and IS in comparison to diabetes patients without IS (9.1 vs. 4.2%,16.4 vs7.4%; P = 0.044,0.044) with OR of 2.29 and 2. 449 respectively (95% CI: 1.024-5.115, 1.024-5.856) but does not withstand Bonferroni correction. Conclusion: A12 containing genotypes and A12 allele are not associated with IR, diabetes and risk of IS development, however, significant higher BMI were observed in A12 allele carriers in the studied patients with diabetes as well as those with IS.

Beta Thalassemia Carrier Rate: Problem Burden among High School Children.

Background & Aim of the Work: ß-Thalassemia (ßT) is highly prevalent in some countries like Egypt. Accurate data about actual disease prevalence and heavily prevalent geographic locations are essential to help in early detection and in setting up effective preventive programs. We aim for screening ßT carriers among Egyptian high school students in the Delta region. SUBJECTS AND METHODS: A cross-sectional multicenter study was carried out on 4320 randomly selected students from four governorates of the Nile Delta region, Egypt. All patients were to be tested for their complete blood count. Those with microcytic hypochromic anemia not caused by iron deficiency were tested for ßT carrier status using high-performance liquid chromatography. RESULTS: The total prevalence of ßT carrier rate was 6.13%. The highest prevalence was detected in Al-Sharkia Governorate, reaching 7.89%, followed by 6.90% in Al-Gharbia Governorate. Al- Dakahilia and Al-Menoufia showed lower rates of 4.86% and 3.73%, respectively. CONCLUSION: Despite the premarital national screening program for ßT in Egypt, the carrier rate is still high. More effort should be done into the proper implementation of national prevention programs.

Circulating Cell-Free DNA and DNA Integrity as Molecular Diagnostic Tools in Hepatocellular Carcinoma.

OBJECTIVES: We assessed the ability to use circulating cell-free DNA (cfDNA) and the DNA integrity index (DNAII) to detect the transition from liver cirrhosis (LC) to hepatocellular carcinoma (HCC). METHODS: Circulating cfDNA and DNAII were measured in 50 patients with advanced LC and 50 patients with HCC who were followed for 1 month after transarterial chemoembolization (TACE). Fifty healthy participants served as a control group. Real-time quantitative polymerase chain reaction (PCR) was used to measure circulating cfDNA concentration, and Alu-PCR was used to measure the concentration of Alu repeats, both short fragments (115 base pairs [bp]) and long fragments (247 bp). We compared liquid biopsy results with the relevant traditional markers. RESULTS: The HCC group showed significantly higher circulating cfDNA concentrations and DNAII values compared with the LC and control groups. No significant differences were found in circulating cfDNA concentrations and DNAII values between the LC and control groups. Circulating cfDNA concentrations decreased significantly after treatment (TACE); areas under the curve of circulating cfDNA concentration and DNAII values were significantly better than those of ɑ-fetoprotein and vascular endothelial growth factor in discriminating between LC and HCC. CONCLUSIONS: The combined use of DNAII with proteins induced by vitamin K absence or antagonist showed better diagnostic performance in HCC. Circulating cfDNA could have a potential role in monitoring HCC treatment.

Prevalence of iron deficiency anemia and beta thalassemia carriers among relatives of beta thalassemia patients in Nile Delta region, Egypt: a multicenter study.

BACKGROUND: Screening of ß thalassemia among close relatives is more feasible in highly prevalent countries with limited resources. The purpose of this study is to determine the prevalence of ß thalassemia carriers and iron deficiency anemia among relatives of ß thalassemia patients in Mid Delta, Egypt. METHODS: This is a cross-sectional multi-center study conducted on 2118 relatives of patients with ß thalassemia from different Egyptian governorates in the Mid Delta region. They were subjected to history taking with precise determination of geographic location, general examination, and the following investigations: complete blood counts, serum ferritin for those who showed microcytic hypochromic anemia, and high-performance liquid chromatography for those who were not diagnosed as iron deficiency anemia. RESULTS: The total prevalence of iron deficiency anemia among close relatives of confirmed ß thalassemia patients in the Nile Delta region was 17.19%. The highest prevalence of iron deficiency anemia (45.05%) was reported in Al-Gharbia Governorate, followed by Al-Menoufia Governorate (21.67%), and the lowest prevalence was that of Al-Sharkia Governorate (4.91%). The differences were highly statistically significant (p < 0.001). ß thalassemia carrier prevalence rate in the studied relatives was 35.84%, with the highest prevalence detected in Al-Sharkia Governorate (51.32%), followed by Kafr-Alsheikh and Al-Dakahilia Governorates (41.78%, 37.13%) respectively, while Al-Menoufia Governorate had the lowest prevalence rate (25.00%). These differences were also highly statistically significant (p < 0.001). CONCLUSION: More than one-third of relatives of patients with ß thalassemia are carriers of the disease, while 17.19% suffer from iron deficiency anemia. This study demonstrates the importance of tracing the high number of beta thalassemia carriers among relatives of patients with ß thalassemia in Egypt.

Serum adiponectin, body adiposity and metabolic parameters in obese Egyptian children with Down syndrome.

OBJECTIVES: Children with Down syndrome (DS) have a higher risk for obesity. Adiponectin plays a crucial role in obesity-related cardiometabolic comorbidities. The study aimed to explore whether body adiposity indicators, the frequency of metabolic syndrome (MetS) and its components, serum adiponectin and insulin resistance indices as well as the validity of serum adiponectin as a biomarker for MetS are different in prepubertal obese-DS children compared to matched obese-controls. METHODS: Cross-sectional study included 150 prepubertal children classfied into three groups; obese-DS (n=50), obese-control (n=50) and normal-weight-control (n=50). Participants were evaluated for waist-circumference (WC), body adiposity, serum triglycerides, HDL-C, adiponectin and Homeostasis-Model-Assessment of Insulin-Resistance (HOMA-IR). MetS was defined using modified Adult Treatment Panel III-criteria. RESULTS: Obese-DS had significantly higher WC, %body fat, total-fat mass, trunk-fat mass, trunk/appendicular-fat mass ratio, triglycerides, insulin and HOMA-IR and significantly lower HDL-C values compared to obese-control. Higher prevalence of MetS and its components were observed in obese-DS that was evident at younger age. Adiponectin was significantly lower in obese-DS compared with obese-control and in obese-DS children with MetS compared to obesecontrol with MetS. The decrease in adiponectin with increasing grades of obesity was pronounced in obese-DS. Adiponectin exhibited strong correlations with body adiposity, several MetS components and HOMA-IR in obese-DS. Adiponectin performed better as a biomarker for MetS among obese-DS (AUC=0.808) than obese-control (AUC=0.674). CONCLUSIONS: Prepubertal obese-DS displayed excess body adiposity with pronounced central fat distribution, atherogenic lipid profile and higher insulin resistance compared to matched obese-control. Adiponectin performed better as potential biomarker of MetS in obese-DS than obese-control.

VKORC1 and CYP2C9 genotypes in Egyptian patients with warfarin resistance.

Warfarin is the most commonly prescribed anticoagulant drug; however, a narrow therapeutic range and a high risk of bleeding or stroke complicate its clinical use. Warfarin resistance was defined as prolonged warfarin requirements of more than 15 mg/day to achieve therapeutic anticoagulation or failure to achieve therapeutic anticoagulation with more than 20 mg/day. The resistance is associated with polymorphisms of the vitamin K epoxide reductase-oxidase complex (VKORC1) and cytochrome P450-2C9 (CYP2C9) genes, which affect warfarin pharmacodynamics and pharmacokinetics, respectively. Identification of the VKORC1 -1639 (A/G) and CYP2C9 (*1/*2/*3) allelic variants was performed using the PGX-Thrombo Strip in 41 patients with warfarin resistance compared with 30 patients with normal warfarin response out of 352 diagnosed cases of deep vein thrombosis. In warfarin-resistant patients, the VKORC1-1639 genotype frequencies were GG 0.756, GA 0.244 and AA 0.0, whereas in warfarin responder patients, they were: GG 0.333, GA 0.400 and AA 0.276 with P ≤ 0.001. The CYP2C9 genotype frequencies showed nonsignificant difference in both group of patients (P = 0.31). Our results suggest that the VKORC1-1639 GG and the wild type CYP2C9*1*1genotypes are associated with the high-dose requirement for warfarin therapy, and that VKORC1-1639 GG is responsible for warfarin resistance and failure in Egyptian patients.

Atherosclerotic effects of long-term old and new antiepileptic drugs monotherapy: a cross-sectional comparative study.

This work aimed to evaluate the metabolic and atherogenic effects of long-term antiepileptic drugs in a group of Egyptian epileptic patients. Sixty-nine epileptic patients on antiepileptic drug monotherapy for at least 2 years and 34 control subjects were recruited in this study. Patients were divided into 5 subgroups according to antiepileptic drugs used (valproate, carbamazepine, lamotrigine, topiramate, and levetiracetam). Fasting lipid profile (total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol), lipoprotein(a), homocysteine, free thyroxine, thyroid-stimulating hormone, and common carotid artery intima-media thickness were measured for all subjects. Significant higher mean values of low-density lipoprotein cholesterol, low-density lipoprotein / high-density lipoprotein ratio, lipoprotein(a), homocysteine, significantly lower mean value of high-density lipoprotein cholesterol, and significantly larger diameter of common carotid artery intima-media thickness were observed in each drug-treated group versus control group. Our study supports that long-term monotherapy treatment with valproate, carbamazepine, lamotrigine, and topiramate had altered markers of vascular risk that might enhance atherosclerosis, whereas levetiracetam exerted minimal effect.

Low expression of glucocorticoid receptors in children with steroid-resistant nephrotic syndrome.

BACKGROUND: About 10-20 % of children with idiopathic nephrotic syndrome (NS) are steroid-resistant (SR). Low expression of glucocorticoid receptors (GRs) has been associated with poor response to steroids in a variety of autoimmune diseases. This study was done to assess the expression of cytoplasmic GRs for CD3 and CD14 in children with NS. METHODS: Expression of cytoplasmic GRs in lymphocytes (CD3(+)/GR) and monocytes (CD14(+)/GR) in the peripheral blood were assessed in 51 children with NS before the start of therapy by flow cytometry. Patients were divided into two groups: 30 children who were steroid-sensitive (SSNS) and 21 children who had initial steroid resistance (SRNS). Twenty age- and sex-matched healthy children served as controls. RESULTS: Expression of CD3(+)/GR was significantly lower in SRNS in comparison to SSNS patients and controls (p < 0.0001). Similarly, expression of CD14(+)/GR was significantly lower in SRNS in comparison to SSNS patients (p < 0.0001) and controls (p = 0.002). CD3(+)/GR and CD14(+)/GR expression were not significantly different in SSNS patients compared with controls (p = 0.06 and 0.07 respectively). CONCLUSIONS: Patients with initial SRNS showed decreased GR expression in peripheral blood mononuclear cells (PBMC) before starting therapy, and this low expression may be one of the pathophysiological mechanisms of steroid resistance in these children.

Leptin, insulin and thyroid hormones in a cohort of Egyptian obese Down syndrome children: a comparative study.

BACKGROUND: Obesity is a major worldwide health problem. It is commonly observed in Down syndrome individuals than in the general population. The reason for increased risk of obesity in DS is unclear.The current study was designed to clarify differences in some obesity- related hormones in a group of prepubertal Down syndrome children. METHODS: Thirty six Egyptian children with Down syndrome were enrolled in this study, divided according to their body mass index (BMI) into 23 obese and13 non obese. Another group of 43 non Down children were recruited, they were divided according to their BMI into 20 patients having simple obesity and 23 non obese, as control groups. Fasting blood samples were collected for estimation of fasting blood glucose (FBG), insulin, leptin, free thyroxin (FT4), thyroid stimulating hormones (TSH) and creatine kinase (CK). Insulin resistance was assessed by Homeostasis Model Assessment method (HOMA-IR). The ratio of leptin to BMI (LEP/BMI) was used as an index of leptin resistance. RESULTS: Median values of FBG, insulin, and HOMA-IR were significantly higher in Down versus non Down groups, while median values of leptin and leptin resistance were non-significantly different among Down versus non Down groups. Median TSH values were non- significantly different between obese Down and obese non Down. Although the median values of TSH and FT4 were within normal range in Down groups, four cases of subclinical hypothyroidism were encountered. Leptin levels were correlated with insulin and IR but not with TSH in Down groups. CONCLUSION: Increased circulating leptin, a marker of leptin resistance in obese children with Down syndrome seems to be similar to that in children with simple obesity. Elevated FBG and insulin in obese Down children highlights the presence of early IR. Associated myopathy evidenced by mildly elevated CK levels could be an added factor for obesity in such group of patients.