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ABSTRACT: Background: Crohn's disease (CD) and ulcerative colitis (UC) are two major clinical presentations of inflammatory bowel disease (IBD). Many novel candidate genes have been found to be associated with increased risk for IBD. Recently IL-23 receptor gene is identified as an IBD associated gene in genome-wide studies. Objective: To ascertain whether rs7517847 and rs1004819 SNPs in the IL-23 receptor gene are associated with UC in our population in Kerman, south east of Iran. Methods: A total of 85 patients with UC and 100 healthy controls enrolled in our study. Endoscopic procedure was performed for all patients to determine their disease severity. IL-23 receptor genotyping at positions rs7517847 and rs1004819 was done by PCR-RFLP technique. Results: The results of this study showed no association between the studied polymorphisms in the IL-23 receptor gene and UC in our population. However, we found a significant association between rs7517847 gene polymorphism in IL-23 receptor and two important clinical variables including blood in stool and bowel movements in UC patients. Conclusion: The rs7517847 gene polymorphism in IL-23R may be related to the presence of blood in stool and bowel movements in patients with UC. Further functional analysis with other known IL-23 receptor genotypes and/or other candidate genes is necessary to confirm any genetic association with UC in our population.
Iranian journal of immunology: IJI 06/2012; 9(2):128-35.
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ABSTRACT: Patients with ulcerative colitis are at increased risk of inflammation. Interleukin 23 (IL-23) is a newly identified cytokine with increased expression in inflamed biopsies of colon mucosa in patients with Crohn's disease; however, there is inconsistent evidence on its role in ulcerative colitis.
We aimed to compare serum IL-23 level in patients with ulcerative colitis and normal controls and determine if serum IL-23 level increases with the severity of disease according to endoscopic findings.
We quantified serum IL-23 levels from 60 patients with ulcerative colitis and 20 control individuals. All patients underwent endoscopic procedure to define the severity of disease. Patients were then stratified into 2 groups of "Mild" and "Severe" according to the endoscopic findings.
For comparison of serum IL-23 levels, Platelet count, ESR and CRP between the groups, Mann-Whitney U test and independent sample t test were employed, as appropriate. Pearson's and spearman's correlation tests were employed to test the association of IL-23 with platelet count, CRP and ESR in patients. Our findings showed that serum IL-23 levels were increased in patients with ulcerative colitis compared to normal controls. Moreover, patients in "Severe" group had higher serum IL-23 levels and ESR compared with those in "Mild" group. There was no significant sexual dimorphism in any of studied variables.
We suggest that IL-23 plays an important role in the pathogenesis of ulcerative colitis and is a marker of disease activity in these patients.
Iranian journal of immunology: IJI 09/2011; 8(3):183-8.
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ABSTRACT: The pathogenesis of many diseases is correlated to irregularity in vascular endothelial growth factor (VEGF) expression. Results from several association studies show that variation in the level of VEGF expression is related to polymorphic sequences within the VEGF gene. Additionally, there are many studies showing that some gene polymorphisms significantly influence the pharmacokinetics of immunosuppressive drugs.
The aim of this study was to determine the influence of immunosuppressive drugs on VEGF production in individuals with different VEGF genotypes.
ARMS-PCR was used to genotype VEGF polymorphisms at positions -1154 and -2578 within the promoter of VEGF gene. A VEGF-specific ELISA was used to determine the influence of immunosuppressive drugs on VEGF production in PBMCs of individuals with different VEGF genotypes. Results: Suppressive effect of mycophenolic acid was observed just in individuals with GG -1154/CC -2578, GG -1154/CA -2578 and GA -1154/CC -2578 haplotypes. Additionally, VEGF was significantly suppressed in all individuals after treatment with rapamycin except those who had AA -1154/CA -2578 and AA -1154/AA -2578 VEGF genotype combinations.
Results of a recent study revealed that MMF treatment might be effective in preventing chronic renal rejection only in recipients with IL-10 high producer genotype. Additionally result of another study showed that CYP3A5 genotype markedly influences the pharmacokinetics of rapamycin in kidney transplant recipients. Therefore with regard to our results, different suppressive effect of mycophenolic acid and rapamycin on VEGF production might also be dependent on VEGF genotype.
Iranian journal of immunology: IJI 12/2010; 7(4):217-25.
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ABSTRACT: Vascular endothelial growth factor (VEGF) has a key role in angiogenesis and in transplantation. The level of VEGF is related to the differences in the DNA sequence of its promoter region.
In this study, the association between the combination of VEGF -1154 G and -2578 C alleles and VEGF production by LPS-stimulated PBMCs was investigated. In addition; the relationship between VEGF polymorphisms and the influence of TNF- and IL-4 on VEGF production was studied.
VEGF -1154 G/A and -2578 C/A were detected using ARMS-PCR. To determine the impact of combinations of these two polymorphisms on VEGF production; PBMCs were stimulated by LPS and VEGF production was measured by ELISA.
The combinations of -1154 GG/-2578 CC and -1154 GG/-2578 CA were significantly associated with higher VEGF production (p<0.0001). Production of VEGF was significantly influenced by TNF- in individuals who had certain VEGF genotype combinations. Although VEGF production was dramatically suppressed by IL-4, it was not dependent on VEGF genotype.
Since TNF- has influence on the graft outcome, to avoid allocation of grafts from high TNF- producer donors to recipients, it might be useful to predict and minimize graft rejection by having prior knowledge of TNF- and also VEGF genotypes especially -1154 G/A and -2578 C/A VEGF.
Iranian journal of immunology: IJI 09/2009; 6(3):119-29.
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ABSTRACT: The optimizing and controlling for polymerase chain reactions (PCRs) requires standard target sequences to measure reaction specificity and to obtain accurate gene quantification. However, defined target sequences are often not readily available. This situation is particularly evident in the study of rare splice variant transcripts. For gains in efficiency and reaction speed, a small size of PCR amplicon typifies real-time PCR formats, including hydrolysis probes. This study demonstrates the use of oligonucleotides resembling one strand of complete amplicon sequences used in real-time PCR to provide sustainable and precise amounts of the target sequence without the necessity of enlisting nucleic acid cloning procedures. The application of template oligonucleotides is modeled using all of the splice variant forms of human vascular endothelial growth factor.
Analytical Biochemistry 01/2005; 335(2):299-304. · 3.00 Impact Factor
