الفهرس 
Introduction and the aim of the workOnly 14 pages are availabe for public view
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Abstract
Systemic Lupus erythematosus is a potentially fatal chronic multisystem autoimmune disease. It is more common among females between adolescence and menopause. Defects can happen in many parts of the immune cascade resulting in remarkable heterogeneity of clinical presentations. Both environmental and genetic factors influence the development of the SLE disease.Vitamin D is known as a hormone that regulates bone homeostasis through calcium and phosphorus metabolism. The active form of the vitamin D is strongly regulated and acts through a specific vitamin D receptor (VDR) to mediate its genomics actions on nearly every aspect of calcium homeostasis. Additionally, vitamin D plays a vital role in other metabolic pathways, such as those involved in the immune response.The special biological effects of 1, 25(OH)2 D3, the bioactive form of vitamin D3, are mediated by VDR, which is a member of the superfamily of nuclear hormone receptors, and it is expressed in most cell types. When a ligand binds to VDR, it induces the changes in its conformation which stimulates hetero-dimerization with the retinoid X receptor; the recruitment of co-repressor and co-activator proteins. So, the VDR functions as a ligand-activated transcription factor which binds to vitamin-D-responsive elements in the promoter region of the vitamin-D-responsive gene, and finally affects the rate of RNA polymerase-II-mediated transcription of those genes.In the current study, we investigated BsmI VDR gene polymorphism at position (rs1544410) in intron 8 in children with systemic lupus erythematosus. Also we assessed the oxidative state by measuring serum levels of catalase activity and malonaldehyde, superoxide dismutase, total antioxidant capacity, and glutathione-S-transferase among Egyptian SLE children. We correlated these markers with BsmI VDR gene genotypes and alleles.>We enrolled 100 children with SLE selected from outpatient clinics of Mansoura University Children’s Hospital, Egypt. They included 78 females (78%) and 22 males (22%).The mean age of SLE patients was 10.7±3.7 years. We included 100 healthy children as controls.After extraction of DNA from whole blood, DNA was genotyped for BsmI VDR (rs1544410) gene in intron 8. Detection of the gene polymorphisms was determined using polymerase chain reaction (PCR), and documented using gel electrophoresis system. Gels were electrophoresed for 30 minutes at 100 volts. The gels were then photographed under UV light (320 nm) and scored for the resulting genotype. Peripheral blood was collected and centrifuged for biochemical measurement of oxidative stress markers.The recent data, among Egyptian children with SLE, showed that the genotypes frequencies of the BsmI VDR at intron 8 in both SLE patients and controls were within Hardy–Weinberg equilibrium (p ˃ 0.05 for each). BsmI VDR gene polymorphism at intron 8 in SLE patients and control groups The genotypes frequencies of the BsmI VDR at intron 8 were 20% (BB), 43% (Bb) and 37% (bb) in SLE, and 9% (BB), 55% (Bb), 36% (bb) in healthy controls.The frequency of BB genotypes was significantly higher in SLE patients in comparison to controls (p = 0.04; OR = 2.5 and 95%CI = 1.01 - 5.9). There was no significant difference between B-allele and b-allele in SLE patients and controls (p = 0.36; OR = 1.2 and 95%CI = 0.8 - 1.8).>Measurement of SOD, GST, TAC, CAT, and MAD levels in SLE patients and control group The analysis of biochemical parameters showed lower levels of SOD, GST and TAC in patients with SLE than healthy controls. The results indicated highly significant difference in SOD and GST in SLE patients compared to controls {172.5(18.75-232.5) vs. 291.6 (144.9-366.4); p ≤ 0.001}, {0.02 (0.01 - 0.12) vs 26.4 (1.9 - 50.9); p ≤ 0.001} and {0.9 (0.1 -1.7) vs. 1.03 (0.2 - 1.9); p = 0.95}; respectively. The CAT activity and MAD levels were significantly increased in patients with SLE than control groups {428 (142 - 857) vs. 260.7 (40 - 731); p ≤ 0.001}, {0.59 (0.11 - 0.98) vs 0.43 (0.02 - 0. 9); p ≤ 0.001}; respectively. Association between BsmI VDR gene polymorphism at intron 8 and the oxidative stress parameters of SLE patients No significant differences were detected between BB, Bb and bb genotypes and oxidant or antioxidant parameters with any SLE patients. Similarly, No significant differences were detected between B-allele; b-allele and oxidant or antioxidant parameters with any SLE patients.from our study, we concluded that the BB genotype of BsmI VDR gene could be associated with SLE susceptibility in Egyptian children. Also, from our data, where support the fact that imbalance in the redox state plays an active role in the pathogenesis of SLE.