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Abstract
SUMMARY AND CONCLUSION
AD has been linked to several gene clusters on multiple chrosomes that are associated with elevated IgE level and ashma. Interestingly, these gene loci are in close proximity to loci linked to psoriass and some other skin diseases (Shaw, 2006). IL-13 gene is located at the chromosome 5q31-33 region where both linkage and association studies have previously provided evidence for susceptibility genes for AD, bronchial hypersensitivity, asthma and total serum IgE levels (Ober et al., 1998). The aim of this work was to identify the allelic distribution of G4257A and G4738A polymorphisms of IL-13 in atopic dermatitis patients, their relationship with atopic markers and the functional impact of SNP/SNP interaction within the same gene. This study was carried out in Outpatient Clinic of the Dermatology and Venereology department, Faculty of at Medicine, Zagazig University. The study included 25 patients with atopic dermatitis of both sexes with an age ranging from 8-22 years and 13 normal control subjects (age and sex matched). All patients met the diagnostic criteria for atopic dermatitis, as defined by Hanifin and Rajka. (1980). None of those patients had other atopic conditions (asthma, rhinitis or conjunctivitis) nor received antihistamines, or systemic or topical corticosteroids during the period of the last 3 weeks before clinical evaluation. The severity of atopic dermatitis was measured by using the SCORAD index. AD was considered mild, moderate, and if the SCORAD index was less than 25, between 25 and 50 and 50 respectively. Both patients and healthy control were subjected for the following assessment: • Full history taking and clinical examination.• Stool & urine analysis to exclude parasitic infestations. • Determination of serum total IgE level by ELISA according to Dorrington and Bennich, (1978). • Determination of serum IL-13 by ELISA according to Huang et al. (1995).• Determination of Arg 130GIn polymorphism by PCR-based restriction fragment length polymorphism (RFLP) according to Graves et al. (2000). • Detection of IL-13 gene polymorphism at +4738 by PCR-based RFLP according to Howard et al. (2001). The results of the current study can be summarized as follows: There was a significant association of genotyping and allele frequencies of G4257A polymorphism in atopic dermatitis patients when compared with controls, A4257 allele frequency was 28% (p<0.05) with odd ratio 4.85 (p<0.05). While there was no significant difference in genotyping and allele frequencies of IL-13 gene polymorphism at + 4738 in these groups when compared with controls, A4738 alle frequency was 18% (p>0.05). The mean values of serum level of total IgE, serum IL-13 were and allelic variants of both G4257A and G 4738A polymorphisms were significantly different in atopic dermatitis patients (p<0.05). There was significant increase in the total serum IgE and serum IL-13 level towards homozygos A/A than the homozygos G/G for each group. >Our results showed that there was a significant association between G4257A and G4738A polymorphisms of IL-13 in all atopic dermatitis patients whereas there was no significant association between them in control. This indicated that significant linkage disequiliprium was observed between the two SNP-IL-13 variants. When studying the relation of G4257A polymorphism with the disease severity, our results revealed no significant difference in allele or genotype frequencies between atopic dermatitis patients with mild disease and those with severe disease. In the present study, serum levels of IL-13 and total IgE were significantly higher in atopic patients as compared with control. There was no significant association between serum IL-13 level and severity of the disease in atopic dermatitis patients (P>0.05) but concerning with serum IgE, there was highly significant association with the disease severity (p<0.001). In our study, there was a significant positive correlation between serum IL-13 level and total serum IgE level of atopic patients. In conclusion the elevation of IL-13 and total IgE level in sera of atopic dermatitis patients and the positive correlation between them support the effect of IL-13 on induction of IgE and its role in the pathogenesis of AD. Our results suggested that IL-13 gene polymorphism at +4257 (Arg 130Gln) have been contributed to the suscibility to AD and this indicated a relatively modest change in function from a single nucleotide polymorphism that can result in an important biological difference. Although G4738A variant of IL-13 has not been associated with atopic dermatitis, significant relation between it and G4257A and this may indicate its synergistic effect on G4257A polymorphism for IL-13 dependent gene induction. To generalize, G4257A polymorphism of IL-13 (Arg 130Gln) may be an important determinant of susceptibility of AD elevated total serum IgE phenotype in Egyptians, to confirm this opinion further studies with more patients numbers is required. Finally, the identification of variants of IL-13 gene signaling in the development of AD in humans provides a focus for the development of diagnostic and therapeutic strategies.