ABSTRACT
Ulcerative colitis [UC] is a multi-factorial autoimmune disease. P-glyco-protein is encoded by the multidrug resistance 1 [MDR1] gene. The C3435T polymorphism in the MDR1 gene is correlated with low P-glycoprotein expression. Additionally, vitamin D has regulatory effects on the immune system. The aim of our study was to determine the association between the C3435T MDR1 polymorphism and UC and to detect the vitamin D serum levels in patients with UC. One hundred healthy controls and 85 patients with UC were evaluated. Polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] was used to detect the C3435T MDR1 polymorphisms. Serum levels of vitamin D were measured by Enzyme-linked immunosorbent assay [ELISA]. The research was performed in Kerman, Iran, from 2011 to 2013. We could not find any association between the C3435T MDR1 polymorphism and susceptibility to UC. There was a significant decrease in serum levels of vitamin D in patients with UC compared with healthy controls [p<0.001]. Controversies regarding the association between the C3435T MDR1 polymorphism with UC have been reported in different populations. The difference between our results and others may be attributed to the heterogeneity of the Iranian population and the sample size. Additionally, our data indicated that UC might be correlated with vitamin D insufficiency. Therefore, the administration of vitamin D might be suggested as a valuable treatment for patients with UC
ABSTRACT
The autism spectrum disorders [ASD] are amongst the most heritable complex disorders. Although there have been many efforts to locate the genes associated with ASD risk, many has been remained to be disclosed about the genetics of ASD. Scrutiny's have only disclosed a small number of de novo and inherited variants significantly associated with susceptibility to ASD. These only comprise a small number of total genetic risk factors. Some studies confirm the contribution of mitochondrial genome mutations to the pathophysiology of the autism, but some other studies rejected such a contribution. In the current study we tried to scrutinize the association between mitochondrial tRNA genes mutations and the risk of Autism. DNA was extracted from the blood of 24 patients with ASD and 40 age-matched healthy controls from Special Medical Center in Tehran. 22 tRNA genes of mitochondrial genome were PCR amplified using 12 primer pairs and sequenced. Sequencing results were searched for mutations using clustalW Progran and then the association of mutations with the autism risk was assessed by statistical analysis using SPSS version 15. Many of the observed mutations were sporadic mutations without any significant relationship with the risk of autism, and the other mutations including those of high frequency showed no significant relationship with the risk of disease as well [P>0.05] except mutations 16126T>C [P=0.01], 14569G>A[P=0.02] and 1811A>G[P=0.04]. These three mutations were in the noncoding regions of the mitochondrial genome near tRNA genes. The mutation 16126T>C was in the mtDNA control region. Our study showed a significant relationship between the point mutations 16126T>C, 14569G>A and 1811A>G of the mitochondrial genome and the risk of autism
ABSTRACT
Inflammatory bowel disease, an autoimmune disease, has two clinical manifestations including Crohn's disease and ulcerative colitis [UC]. IL-17 has been the target of intensive research in autoimmune diseases. The influence of Toll like receptor 4 [TLR-4] gene polymorphisms on IL-17 production has also been revealed in UC patients and tissue inflammation in mice. To investigate the association between the TLR-4 gene polymorphisms, Asp299Gly and Thr399Ile and IL-17 serum levels with ulcerative colitis. Additionally, we aimed to study modulation effects of forenamed gene polymorphisms on IL-17 serum levels in UC patients and controls. A total of 256 healthy controls and 85 UC patients enrolled in our study. DNA was extracted and PCR-RFLP technique was employed to determine Asp299Gly and Thr399Ile polymorphisms in TLR-4 gene and IL-17 serum levels were measured by ELISA method. There was no significant difference between the frequency of Asp299Gly A>G and Thr399Ile C>T in UC patients and controls. While IL-17 serum levels in UC patients were significantly higher than controls [p=0.003], no significant difference in IL-17 levels between different genotypes existed. Additionally, a significant inverse relationship was observed between hemoglobin level and IL-17 serum levels in UC patients [p=0.039]. Increased IL-17 serum levels in our UC patients might be explained through the synergistic activity of IL-17/IL-23 axis and pro-inflammatory cytokines, causing severe clinical outcome in patients with IBD. The prolonged excretion of blood in stool driven by inflammatory process which causes iron metabolism disorder and anemia may elucidate the inverse correlation between hemoglobin and IL-17 serum levels in UC patients. Lack of association between the TLR-4 gene polymorphisms and UC in our study was consistent with the results from other Caucasian populations
ABSTRACT
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. 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. 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. 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. 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