Association of Interleukin-6 and Interleukin-1 Family Gene Polymorphisms in Autoimmune Hepatitis.

INTRODUCTION AND AIM: Autoimmune hepatitis (AIH) is an immune-mediated destruction of liver cells, in recognition of interface hepatitis, seropositivity for autoantibodies, and interface hepatitis in histology sections. Hepatocyte destruction in AIH is the direct result of CD4+ T-cell destruction. Yet, Th17 mediated immune attach and a diversity of cytokine networks, including pro-inflammatory cytokines such as Interleukin 1 (IL-1) and Interleukin 6 (IL-6), set the stage for the destructive liver damage. MATERIAL AND METHOD: Peripheral blood samples from 57 patients, with AIH, recruited from referrals to the main pediatric hospital in Tehran. Single nucleotide polymorphisms for the following cytokines genes, were evaluated through, polymerase chain reaction with sequencespecific primers (PCR-SSP) assay: IL-1a (C/T -889), IL-1α (C/T -511), IL-1ß (C/T +3962), IL-1 receptor (IL-1R; C/T Pst-I 1970), IL-1RA (C/T Mspa-I 11100), and IL-6 (C/G -174 and A/G nt565). RESULTS: Significant higher frequency of genotype AA was detected in patients in IL-6 at position nt565 (15.8% in AIH patients vs. 2.9% in controls, p = 0.003). The haplotype GA of IL-6 at -174 and nt565, was significantly overrepresented in the AIH group, compared to (20.9% of AIH vs. 1.4% in controls p < 0.0001). CONCLUSION: Results of our study, indicate significant deviation toward high yield IL-6 polymorphisms, in AIH patients. These data could bring new insights in pathophysiology of disease, which could contribute to developing novel treatments for AIH.

Interleukin-2, Interferon-gamma Gene Polymorphisms in Recurrent Aphthous Stomatitis.

Recurrent aphthous stomatitis (RAS) is the most common oral ulcerative inflammatory disease with unknown etiology. IL-2 and IFN-γ are secreted by Th1 cells and the elevated levels of them have been reported in RAS. Single nucleotide polymorphisms (SNPs) of IL-2 and IFN-γ genes could alter the cytokine production. The aim of this study was to investigate frequencies of IL-2 and IFN-γ alleles and genotypes in a group of patients with minor-RAS (MiRAS). PCR-SSP method used to type genomic DNA of 64 Iranian patients with MiRAS for IL-2 gene (G -330 T) and (G +166 T) and IFN-γ gene at position UTR5644 (A/T). Frequency of each allele and genotype was compared with control group. IL-2 +166 G allele was significantly lower among patients which was reflected in significantly decreased of GG genotype at this position, while IL-2 +166 T allele was significantly higher among patients, IL-2 GT genotype was also significantly higher in RAS patients. No significant differences were found regarding IL-2 -330 G/T allele frequencies, while IL-2 GT genotype at this position was significantly higher among patients and IL-2 -330 TT genotype was significantly lower among RAS patients. Although no significant differences were found in IFN-γ allele frequencies at UTR5644 (A/T), AT genotype at this position was significantly overrepresented among patients compared with controls. Results of this study suggest that certain SNPs of IL-2 and IFN-γ genes have association with predisposition of individuals to RAS. More studies in different ethnic groups are needed to confirm results of this study.

NLRP3 gene polymorphisms in Iranian patients with recurrent aphthous stomatitis.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is a common disorder with an unclear etiopathogenesis. Involvement of the immune system in the development of this condition is strongly suggested. As the variations in the inflammasome-related NLRP3 gene have been suggested to affect immune system activity, this case-control study was performed to determine whether these genetic variants are associated with RAS. METHODS: We studied a group of 69 Iranian patients with RAS in comparison with 56 healthy controls. We determined four single nucleotide polymorphisms (SNPs) of NLRP3 and performed association analyses of NLRP3. Genotyping was conducted using the TaqMan method. RESULTS: The NLRP3 rs3806265 T allele was significantly more frequent in the patients with RAS than in the healthy controls (P = 0.003). While a significant negative association was found between the C allele at the same position with RAS (P = 0.003), the TT genotype was significantly more frequent at position rs3806265 in NLRP3 in patient group than in the controls (P = 0.002). However, the frequency of CT genotype at the same position was significantly higher in healthy controls than in the case category (P = 0.002). CONCLUSIONS: Considering the high frequency of the presence of NLRP3 rs3806265 TT genotype in patients with RAS, it seems that this gene polymorphism could affect individual susceptibility to RAS.

Variation in the miRNA-433 binding site of FGF20 is a risk factor for Parkinson's disease in Iranian population.

DNA variations in the fibroblast growth factor 20 gene have been reported to be associated with Parkinson's disease (PD). The rs12720208, a functional SNP located in the 3'UTR region of the gene, was reported as a risk factor for PD. A number of studies, which tried to replicate the result in different populations, failed to detect any associations. In this study, we genotyped rs2720208 SNP in 520 PD patients and 520 healthy controls both from Iran. Significant differences were found in allele and genotype frequencies between patients and controls (p<0.0001 for both). Our results suggest that the rs12720208 polymorphism may be a risk factor for PD in Iranian population.

Interleukin-10 gene polymorphisms in recurrent aphthous stomatitis.

Recurrent aphthous stomatitis (RAS) is a common oral inflammatory disease with unknown etiology in which the immune system seems to have a role in oral tolerance. Interleukin (IL)-10 is a cytokine synthesis inhibitory factor. Single nucleotide polymorphisms (SNPs) of IL10 gene could alter this cytokine production. The aim of this study was to investigate frequencies of IL10 alleles and genotypes in a group of individuals with RAS. Genomic DNA of 60 Iranian patients with RAS were typed for IL10 gene (C/A -1082, C/T -819, and C/A -592), using PCR-SSP method. Frequency of each allele and genotype was compared to control group. A significantly higher frequencies of the T allele at position -819 (p=0.006) and the A allele at position of -592 (p<0.001) were found in the patients with RAS group, when compared to the controls. IL10 GA genotype at position -1082 (p=0.007), CA genotype at position -592 (p=0.001), and CT genotype at position -819 (p=0.001) were significantly higher in the RAS patients. The results of this study suggest that certain SNPs of IL10 gene have association with predisposition of individuals to RAS. However, further multicenter studies should be conducted to confirm the results of this study.

Association of interleukin 10 and transforming growth factor ß gene polymorphisms with chronic idiopathic urticaria.

Transforming growth factor ß (TGF-ß) and interleukin 10 (IL-10) are two anti-inflammatory cytokines that are implicated in the pathogenesis of urticaria. The goal of this study was to examine the possible association of polymorphisms of TGF-ß and IL-10 genes with susceptibility to chronic idiopathic urticaria (CIU). This study was conducted on 90 patients with CIU. Polymerase chain reaction (PCR) was done to determine the genotype at 5 polymorphic sites; TGF-ß (codon10C/T and codon25G/C) and IL-10 (-1082G/A, -819C/T, and -592C/A). The C allele at codon 25 of TGF-ß was more prevalent in CIU patients compared to controls (OR = 9.5, 95% CI = 5.4-16.8, P<0.001). Genotypes of CT and CG at 10 and 25 codons of TGF-ß gene, respectively, and AG, CT, and CA for loci of -1082, -819, and -592 of IL-10 gene were significantly higher in CIU patients (P<0.001). In haplotype analysis, frequency of TGF-ß haplotypes differed between patients with CIU and controls; CC haplotype was overrepresented, while CG and TG haplotypes were underrepresented (P<0.001). These results suggest that TGF-ß and IL-10 genetic variability could contribute to susceptibility to CIU. Additionally, patients with CIU seem to have genotypes leading to high production of TGF-ß and IL-10.