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.

Prognostic significance of the genetic variant of lymphotoxin alpha (p.Thr60Asn) in egyptian patients with advanced hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide in terms of mortality, and susceptibility is attributed to genetic, lifestyle, and environmental factors. Lymphotoxin alpha (LTA) has a crucial role in communicating the lymphocytes with stromal cells and provoking cytotoxic effects on the cancer cells. There are no reports on the contribution of the LTA (c.179 C>A; p.Thr60Asn; rs1041981) gene polymorphism to HCC susceptibility. The main aim of this study is to investigate the association of LTA (c.179 C>A; p.Thr60Asn; rs1041981) variant with the HCC risk in the Egyptian population. METHODS: This case-control study included 317 participants (111 HCC patients, and 206 healthy controls). The LTA (c.179 C>A; p.Thr60Asn; rs1041981) polymorphism was assessed by tetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) technique. RESULTS: The frequencies of the dominant and recessive models (CA + AA; AA) of the LTA (c.179 C>A; p.Thr60Asn; rs1041981) variant were statistically significant among HCC patients in comparison to controls (p = 0.01; p = 0.007; respectively). The A-allele of LTA (c.179 C>A; p.Thr60Asn; rs1041981) variant was statistically significant in HCC patients in comparison to controls (p ˂ 0.001). CONCLUSION: The LTA (c.179 C>A; p.Thr60Asn; rs1041981) polymorphism was independently associated with an increased risk for hepatocellular carcinoma in the Egyptian population.

MUC7 VNTR polymorphism and association with bronchial asthma in Egyptian children.

Overproduction of mucins in the airways donates largely to airway blockage in asthma patients. Glycoprotein MUC7 plays a role in the clearance of bacteria and has anti-candidacidal criteria. Our goal was to investigate the association between the MUC7 variable number of tandem repeats (VNTR) polymorphism and bronchial asthma among Egyptian children. The MUC7 VNTR polymorphism was investigated among 100 children with bronchial asthma and 100 healthy controls using polymerase chain reaction (PCR) method. Serum levels of immunoglobulin E (IgE), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta1 (TGF-ß1) were assessed by enzyme-linked immunosorbent assay (ELISA) technique. The frequencies of 6*5 genotype, 5*5 genotype, (6*5 + 5*5) genotypes, and MUC7*5 allele of the MUC7 VNTR variant were significantly lower among asthmatic patients than controls (p < 0.015, OR = 0.39, 95% CI = 0.19-0.81; p = 0.03, OR = 0.18, 95% CI = 0.04-0.86; p < 0.001, OR = 0.29, 95% CI = 0.15-0.58; p < 0.001, OR = 0.3, 95% CI = 0.17-0.55, respectively). The (6*5 + 5*5) genotypes of the MUC7 VNTR variant were not associated with the clinical manifestations and serum levels of IgE, TNF-α, and TGF-ß1 among asthmatic patients (p ˃ 0.05). In conclusion, the (6*5 + 5*5) genotypes of the MUC7 VNTR variant may have a protective role for bronchial asthma in Egyptian children.

Genetic variant in the 5' untranslated region of endothelin1 (EDN1) gene in children with primary nephrotic syndrome.

Endothelin-1 plays a crucial role in the pathophysiology of nephrotic syndrome (NS) in children. The primary purpose of this study is to evaluate the contribution of the EDN1 (3A/4A; rs1800997) variant to the risk of nephrotic syndrome. This study involves 200 participants (100 healthy controls, 50 steroid-sensitive nephrotic syndromes [SSNS] patients, and 50 steroid-resistant nephrotic syndromes [SRNS] patients]. Genomic DNA has been characterized using the PCR-RFLP technique. The predominant genotype that is common in this study population was the EDN1 3A/3A genotype (NS [75%] and healthy controls [88%]). The prevalence of EDN1 3A/4A genotype and EDN1 4A allele was significantly increased among NS patients compared with healthy subjects (p-value < 0.05). Furthermore, the frequency of the EDN1 (3A/4A; rs1800997) variant was statistically significant among SRNS patients (p-value < 0.05). The EDN1 3A/4A genotype and the EDN1 4A allele were identified as independent risk factors of the nephrotic syndrome among children.

Livin/BIRC7 gene expression as a possible diagnostic biomarker for endometrial hyperplasia and carcinoma.

BACKGROUND: Livin/BIRC7 is a member of the inhibitors of apoptosis proteins family which are implicated in development of cancer through the inhibition of apoptosis process. This case-control study was intended to investigate livin/BIRC7 gene expression in endometrial hyperplasia and carcinoma and its correlation to some oxidative stress markers in addition to its possible diagnostic performance. METHODS: This study included 90 participants [30 endometrial hyperplasia patients, 30 endometrial carcinoma patients, and 30 healthy controls]. Livin/BIRC7 gene expression was analyzed using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Serum catalase activity was assessed by enzyme-linked immunosorbent assay (ELISA) and malondialdehyde level was measured by the colorimetric method. RESULTS: Livin/BIRC7 gene expression was significantly (p < 0.001) higher in endometrial carcinoma from patients with endometrial hyperplasia when compared to controls. A positive correlation was found between livin/BIRC7 expression and serum catalase activity and malondialdehyde level in endometrial hyperplasia and carcinoma. The detection of livin/BIRC7 in endometrial carcinoma has excellent sensitivity and specificity. CONCLUSIONS: Livin/BIRC7 was overexpressed in endometrial carcinoma with excellent power to differentiate endometrial carcinoma from endometrial hyperplasia or healthy subjects, suggesting that it might be a useful molecular marker for endometrial carcinoma diagnosis.

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.

Polymorphisms of interleukin 4 and interleukin 4 receptor genes and bronchial asthma risk among Egyptian children.

BACKGROUND: Interleukin 4 (IL4) is a key cytokine that regulates the inflammatory cascade in bronchial asthma. We investigated the association between the IL4 and IL4R polymorphisms and the susceptibility for bronchial asthma among Egyptian children. METHODS: IL4 VNTR and IL4R c.1902 A>G p.(Q576R) polymorphisms were investigated among 100 children with bronchial asthma and 100 healthy controls using PCR method. Serum levels of IL4 and immunoglobulin E (IgE) were assessed by ELISA. RESULTS: The frequencies of (A1A2 + A2A2) genotypes and A2-allele of the IL4 VNTR variant were significantly higher among asthmatic patients than controls (p = 0.01, OR = 2.34, 95% CI = 1.24-4.44; p = 0.01, OR = 2.27, 95% CI = 1.29-3.99, respectively). The frequencies of (AG + GG) genotypes and G-allele of the IL4R (A1902G) variant were significantly higher among asthmatic patients than controls (p = 0.003, OR = 2.52, 95% CI = 1.39-4.58; p = 0.002, OR = 2.25, 95% CI = 1.35-3.76, respectively). There was a significant association between (A1A2 + A2A2) genotypes of the IL4 VNTR variant and high serum IL4 level among asthmatic patients (p < 0.001). The (AG + GG) genotypes of the IL4R (A1902G) variant were significantly associated with exposure to triggers, atopic dermatitis and higher serum IgE level in asthmatic patients (p = 0.02, 0.04 and 0.01, respectively). CONCLUSION: IL4 VNTR and IL4R (A1902G) polymorphisms could be associated with higher risks of bronchial asthma among Egyptian children.

Angiotensin II type 1 receptor gene polymorphism and serum angiotensin-converting enzyme level in Egyptian children with systemic lupus erythematosus.

Angiotensin II, the major effective molecule of the renin-angiotensin system, plays a vital role in the development of systemic lupus erythematosus (SLE). To study angiotensin II type 1 receptor (AT1R) gene polymorphism at (A1166C) in Egyptian children with SLE and its correlation with serum ACE level and SLE manifestations. AT1R gene polymorphism (A1166C) was done in 123 children with SLE in comparison to 100 healthy controls using polymerase chain reaction-based restriction fragment length polymorphism method (PCR-RFLP) and the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) to confirm the results of the genotyping. Serum ACE level measurement was done using ELISA technique. The frequencies of C-containing genotypes (AC + CC) and C-allele of AT1R (A1166C) were significantly higher in SLE patients compared to controls (p < 0.0001, OR = 4.9, 95% CI = 2.7-8.8; p Ë‚ 0.0001, OR = 3.6, 95% CI = 2.2-5.9, respectively). Lupus nephritis (LN) patients had significantly higher frequency of (AC + CC) genotypes and C-allele compared with controls (p Ë‚ 0.0001, OR = 5.1, 95% CI = 2.7-9.7; p Ë‚ 0.0001, OR = 3.5, 95% CI = 2.1-6.02, respectively). Mean serum ACE levels were significantly higher in SLE patients compared to controls (p Ë‚ 0.0001). There were no associations between AT1R gene polymorphism and serum ACE level and the clinical manifestations of SLE. The AT1R gene polymorphism can be considered a risk factor for the development of SLE in Egyptian children.