Genetic Variants of Neurotransmitter-Related Genes and miRNAs in Egyptian Autistic Patients

Autism is a neurodevelopmental disorder with indisputable evidence for a genetic component. This work studied the association of autism with genetic variations in neurotransmitter-related genes, including MAOA uVNTR, MAOB rs1799836, and DRD2 TaqI A in 53 autistic patients and 30 healthy individuals. The study also analyzed sequence variations of miR-431 and miR-21. MAOA uVNTR was genotyped by PCR, MAOB and DRD2 polymorphisms were analyzed by PCR-based RFLP, and miR-431 and miR-21 were sequenced. Low expressing allele of MAOA uVNTR was frequently higher in female patients compared to that in controls (OR = 2.25). MAOB G allele frequency was more significantly increased in autistic patients than in controls (P<0.001 for both males and females). DRD2 A1+ genotype increased autism risk (OR = 5.1). Severity of autism tends to be slightly affected by MAOA/B genotype. Plasma MAOB activity was significantly reduced in G than in A allele carrying males. There was no significant difference in patients and maternal plasma MAOA/B activity compared to controls. Neither mutations nor SNPs in miR-431 and miR-21 were found among studied patients. This study threw light on some neurotransmitter-related genes suggesting their potential role in Autism pathogenesis that warrants further studies and much consideration

Influence of Interleukin-6 (174G/C) Gene Polymorphism on Obesity in Egyptian Children

BACKGROUND: Obesity is a multi-factorial chronic disorder. A considerable number of studies have been performed to figure out whether there is an association between obesity and polymorphisms of gene IL-6 (174G/C), but the results are equivocal.AIM: This study aimed to find out whether the IL-6 (174G/C) gene was associated with the risk of developing obesity in Egyptian children.SUBJECTS AND METHODS: The study included 149 children and adolescents with age ranged between 9.5 – 18 years. Eighty-five of them were obese which BMIZ-score is &gt; 2, and sixty-four children with BMIZ-score ≤ 2 served as control group. Serum level of IL-6 and genetic analysis for IL-6 (174G/C) gene polymorphism were done.RESULTS: Obese children had significantly higher serum levels of IL-6 as compared to those of control children (P = 0.003). A high percentage of IL-6 polymorphism GC was found in obese subjects (93.7%), while the control group had a higher percentage of IL-6 polymorphism GG (70.6 %).CONCLUSION: Our study showed that carriers of the C allele for the IL-6 (174G/C) polymorphism have higher BMI. As the G174C polymorphism is likely to affect IL-6 expression and its physiological regulation; consequently this polymorphism may affect adiposity

Apolipoprotein B polymorphism distribution among a sample of obese Egyptian females with visceral obesity and its influence on lipid profile

Background: Regional distribution of adipose tissue is more important than total amount of body fat in predicting complications associated with obesity. Apolipoprotein B (Apo B) plays a central role in lipid metabolism. Aim: To investigate the importance of the XbaI polymorphism of Apo B gene (C7673T) as risk factor for visceral obesity and its influence on lipid profile. Subjects and methods: Total of 122 obese adult females (BMI ⩾ 30 kg/m2): 56 of them with visceral obesity (⩾7 cm by abdominal Ultrasound) and 66 without visceral obesity and 36 age matched non-obese (BMI ⩽ 25 kg/m2) without visceral obesity were studied. Anthropometric assessment, body composition, visceral obesity and lipid profile evaluation were attempted. Genetic analysis of Apo B XbaI was performed using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Results: Visceral obesity was associated significantly with the presence of the heterozygous (CT) genotype of the XbaI Apo B gene (p < 0.001). Frequency of homozygous (CC) was significantly the least genotype found in females with visceral obesity, while homozygote (TT) genotype was more frequent in those without visceral obesity. T allele (about 70%) was more frequent than C allele (about 30%) in all groups. Significant lowest values of visceral obesity, triglyceride and HDL-C were associated with the presence of (CC) genotype and the highest values were associated with the presence of the heterozygous (CT) genotype; except HDL-C with (TT) genotype. Conclusions: Study reveals considerable association of Apo B XbaI gene polymorphism with visceral obesity and some lipid profile parameters (TG and HDL-C) among Egyptian females

Metabolic Implications of Hepatitis C Virus Infection and it's Correlation to Steatohepatitis in Chronic Hepatitis C Patients with and without Type 2 Diabetes

Background Chronic hepatitis C virus (HCV) infection is not a simple viral infection; it has many metabolic and autoimmune complications. Objective To investigate the impacts of chronic HCV infection on glucose and lipid metabolism and its correlation-if any-with body mass index (BMI) and hepatosteatosis in chronic HCV patients. Patients and Methods One hundred and three (103) chronic HCV patients were involved in this study. After blood sugar testing patients were classified into three groups; Group I: 68 chronic HCV patients with type 2 diabetes. Group II: 35 chronic HCV patients without Type 2 Diabetes and Group III: 25 patients with Type 2 Diabetes as a control group. With informed written consents and approval from Ain Shams medical ethics committee, all groups were subjected to the following: full history taking, thorough clinical examination, calculation of BMI, and measurement of the waist/hip ratio were done. Assessment of fasting plasma insulin level was done by the immune-enzymatic method. Assessment of the insulin resistance state was done by Homeostatic Model Assessment (HOMA-IR). Detection of anti-HCV was done by the 3rd generation ELISA test and confirmed by qualitative polymerase chain reaction (PCR). Results Diabetic and non diabetic chronic HCV patients were found to have significantly higher fasting plasma insulin levels and insulin resistance states than the control group. This insulin resistance was not due to increased body mass index as there was a non significant difference in BMI between all the studied groups. Positive correlations were found between plasma insulin level, liver enzymes and steatohepatitis in HCV patients whether they were diabetic or not. No correlation was found between BMI and plasma insulin level in group II patients (HCV only). Conclusion Chronic HCV infection may be regarded as an independent risk factor for the development of insulin resistance and type 2 diabetes. HCV induces insulin resistance; the key step for glucose intolerance, and virus C induced steatohepatitis therefore leading to faster progression to cirrhosis. The impacts of chronic HCV infection on glucose and lipid metabolism should be recognized in clinical care centers and addressed in future studies

Genetic and Epigenetic Regulation of MEFV Gene and Their Impact on Clinical Outcome in Auto-Inflammatory Familial Mediterranean Fever Patients

Epigenetic modifications play a pivotal role in autoimmune/inflammatory disorders and could establish a bridge between personalized medicine and disease epidemiological contexts. We sought to investigate the role of epigenetic modifications beside genetic alterations in the MEFV gene in familial Mediterranean fever (FMF). The study comprised 63 FMF patients diagnosed according to the Tel Hashomer criteria: 37 (58.7%) colchicine-responders, 26 (41.3%) non-responders, and 19 matched healthy controls. MEFV mutations were detected using a CE/IVD-labeled 4-230 FMF strip assay. DNA methylation of MEFV gene exon 2 was measured using bisulfite modification and related to pyrin level, phenotypic picture, MEFV mutations, disease severity, serum amyloid A (SAA), CRP, ESR, disease severity, and colchicine response. Our results showed that FMF patients exhibited significantly higher methylation percentage (p p p < 0.004). High methylation percentage of the MEFV exon 2 and low pyrin concentration were correlated with disease severity, high SAA, ESR levels, H-pylori, and renal calculi. In conclusion, this study highlights the relation between high methylation percentage, reduced pyrin level, and different biomarkers in FMF, which underscores their role in the pathogenesis of FMF and could be considered as potential therapeutic targets