Fibroblast Growth Factor-2 Levels are Elevated in The Serum of Patients with Multiple Sclerosis

BACKGROUND: Various factors contribute to the pathogenesis of Multiple Sclerosis (MS), one of which is Fibroblast Growth Factor 2 (FGF2). The function of FGF2 is pleiotropic. The investigation of the role of this factor in the myelination has produced conflicting results. OBJECTIVE: To investigate the serum levels of FGF2 in patients with MS. SUBJECTS AND METHODS: Eighty patients with MS and eighty healthy volunteers with no history of inflammation or demyelinating disorders were included, and serum samples were collected to evaluate serum levels of FGF2 using the ELISA technique. Both groups had the same age and gender distribution. For analysis, the Mann-Whitney U test was used. RESULTS: Patients with MS had considerably greater serum FGF2 levels than the control group (p = 0.005). There was no difference between the FGF2 level in men and women. CONCLUSION: Our data indicate that FGF2 levels may be related to the susceptibility of Iranian patients with MS. Further studies are required to analyze the involvement of FGF2 in enhancing the inflammatory process in MS.

Association study of M235T and A-6G polymorphisms in angiotensinogen gene with risk of developing preeclampsia in Iranian population.

OBJECTIVE: Preeclampsia (PE) is a life-threatening complication of pregnancy that accounts for 12% of all maternal deaths worldwide. The aim of this study is to investigate the relationships between the polymorphisms of angiotensinogen (AGT) gene and preeclampsia. MATERIAL AND METHODS: In this study, 240 unrelated preeclampsia patients and 178 normotensive women were examined. Genomic DNA was extracted then we assessed M235T(C/T) and A-6G polymorphisms of the AGT gene. Genotyping of M235T and A-6G polymorphisms were performed using SSP-PCR and MS-PCR, respectively. RESULTS: A significant protective association was observed between A-6G G allele, A-6G A/G heterozygote genotype (OR = 0.6, p = 0.007 and OR = 0.6, p = 0.04) against PE. Furthermore, it was shown that two copies of A-6G A allele would increase PE risk (OR: 0.62, p = 0.04). Our results did not show a significant association for M235T polymorphism and PE. However, the combinations of A-6G A/A genotype and M235T T/C genotype (OR = 0.4, p = 0.02) and also A-6G A/G genotype and M235T T/C genotype (OR = 0.5, p = 0.04) in controls represented a significant protective association against PE. CONCLUSION: According to the existence of significant correlation between two candidate polymorphisms, A-6G and M235T polymorphisms, with PE disease in our study, they may be considered as valuable factors in susceptibility to PE disease in Iranian women.

Interleukin-6 Genetic Variation and Susceptibility to Gastric Cancer in an Iranian Population

Background: Despite recent decrease in the incidence of gastric cancer, it is still a common type of cancer in the north of Iran. Many evaluations have shown that polymorphisms of cytokine genes like that for interleukin 6 (IL-6), which play important roles in regulation of the immune response, can increase the risk of gastric cancer. This study examined the role of the IL-6-174 gene polymorphism in susceptibility in an Iranian population. Method: Genomic DNA was extracted from peripheral whole blood of 100 patients and 361 healthy controls. Genotyping was accomplished by the sequence-specific primer-polymerase chain reaction (SSP-PCR) method and statistical analyses were carried out using Fisher's exact test. Frequencies of the IL-6-174 G/C genotypes were determined under co-dominant, dominant, and recessive genetic models. Results: An association between the polymorphism of IL-6 -174 G/C and susceptibility to gastric cancer was observed. The frequency of G allele was higher in patients (78%) than in controls (70.5 %) (OR=1.48, 95% CI=1.01-2.20, P=0.04). Conclusions: The high G allele and G/G genotype frequency in patients compared to control subjects suggests that the IL-6 -174 G/C polymorphism may influence the susceptibility to gastric cancer. In addition, the demographic information showed that most of the subjects were male (69.0%) that gastric cancer is related to environmental factors.

Combination of Myelin Basic Protein Gene Polymorphisms with HLA-DRB1*1501 in Iranian Patients with Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS), as a multifactorial autoimmune disease with complex genetic basis, causes demyelination in the central nervous system via cytokine responses to myelin antigens. Myelin basic protein (MBP) is the main protein component of the myelin sheath. HLA-DRB (human leukocyte antigen-DR beta) alleles, particularly HLA-DRB1*1501, may be of significance in the pathogenesis of MS. OBJECTIVE: To examine the association of HLA-DRB1*1501 alleles and MBP VNTR (variable number tandem repeat) polymorphism with the MS susceptibility in Iranian population. METHODS: Genomic DNA was extracted from peripheral blood. The alleles were determined by the Polymerase Chain Reaction (PCR) method in 259 MS patients and 312 healthy control individuals and analyses were carried out using Fisher's exact test. RESULTS: The frequencies of MBP VNTR genotypes (AA, AB and BB) were 47%, 42% and 11% among patients, and 45%, 43% and 12% in control subjects, respectively. HLA-DRB1*1501 allele was more frequent among patients than healthy individuals (OR=1.65, P=0.0045). The frequency of allele A and genotype A/A was significantly higher among HLA-DRB1*1501 positive patients (61% and 32%) than controls (46% and 19%) (OR=1.88, P=0.0013; A/A vs. B/B: OR=5.09, P=0.0004). The two-locus analysis of the interaction between the MBP VNTR polymorphism and the HLA-DRB1 allele showed that the HLADRB1* 1501/A haplotype was more frequent among MS patients than the healthy controls. CONCLUSION: The interaction between the HLA-DRB1*1501 allele and MBP gene may be considered as a predisposing factor in the development and pathogenesis of MS in the case of gene-gene interaction.

Tumor Necrosis Factor Alpha 308 G/A Single Nucleotide Polymorphism and Susceptibility to Hepatocellular Carcinoma Via Hepatitis B Infection.

BACKGROUND: Hepatitis B virus (HBV) is a key factor for hepatocellular carcinoma (HCC). About 350 million people are affected by chronic infection which is related to the rapid development of liver diseases as well as hepatitis, cirrhosis and hepatocellular carcinoma. Expression of tumor necrosis factor alpha (TNFα) in the liver demonstrates a major genetic polymorphism which is involved in resistance or susceptibility to chronic HBV infection. MATERIALS AND METHODS: In this study, two populations were studied by the sequence specific primerpolymerase chain reaction (SSPPCR) method: HBV cases (n=409), who were HBSAg+, and healthy controls (n=483). RESULTS: The results shown that the frequency of TNFα 308 G/G genotype in healthy controls (47.2%) was significantly higher than in HBV infected patients (28%) (CI = 1.292.61, OR = 1.83, P = 0.0004). Also TNFα 308 A/A and A/G genotype frequencies in the healthy controls were 4.6% and 48.2% and in patient group were 19.5% and 52.5% (CI = 2.237.12, p: 0.0001, OR: 3.94) respectively. CONCLUSIONS: We found that among Iranian people TNFα 308A allele not only has the highest genotype frequency but also it has the highest frequency in the world population. In addition, TNFα308 G/G polymorphism was associated with HBV resistance, whereas TNFα308A (A/A or A/G) polymorphism appeared to associated with chronic HBV infection. These data suggested that among the Iranian population, the 308 G/G polymorphism of TNFα gene promoter region has the potential to influence the susceptibility to HBV infection and it may be responsible for viral antigen clearance.

Interleukin-6-174 Promoter Polymorphism and Susceptibility to Hepatitis B Virus Infection as a Risk Factor for Hepatocellular Carcinoma in Iran.

BACKGROUND: Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). Cytokines play an important role in the regulation of immune responses and defense against viral infections. Human interleukin 6 (IL6) is a multifunctional cytokine that participates in these processes. OBJECTIVE: The aim of this study was to assess the IL6-174 gene polymorphism in patients with chronic hepatitis B virus (HBV) infection as compared with healthy controls in an Iranian population. MATERIALS AND METHODS: Totals of 297 HBV patients and 368 control individuals were evaluated. Genomic DNA was extracted from peripheral blood and the SSP-PCR (sequence specific primer-polymerase chain reaction) method was applied for genotyping. RESULTS: The frequencies of genotypes C/C, G/G and C/G in HBV cases were 4.7%, 34.3%, 60.9% and in controls were 12.8%, 39.7% and 47.6%, respectively. The frequencies of G and C allele in patients and controls were 78.1%, 21.9% and 67.4%, 32.6 % respectively. There was a significant difference in the frequencies of G/G genotype (CI=1.8-7.1, OR=3.47, P=0.00001) and G allele (CI=1.34-2.23, OR=1.72, P=0.0001) between HBV patients and the control group. CONCLUSIONS: These findings suggest that the IL6-174 C/G genotype and the G allele are strongly associated with susceptibility to HBV infection. Demographic information showed that most of the subjects were male (74.4%). According to high frequency of G/G genotype in male participants (63.1%) men probably are more susceptible to hepatitis than women.

Effects of date palm fruit extracts on skin mucosal immunity, immune related genes expression and growth performance of common carp (Cyprinus carpio) fry.

The aim of this study was to investigate the effects of date palm fruit extracts (DPFE) on skin mucosal immunity, immune related genes expression and growth performance of fry common carp (Cyprinus carpio). One hundred and twenty specimens (4.06 ± 0.13 g) were supplied and allocated into six aquaria; specimens in three aquaria were fed non-supplemented diet (control) while the fish in the other 3 aquaria were fed with DPFE at 200 ml kg(-1). At the end of feeding trial (8 weeks) skin mucus immune parameters (total immunoglobulins, lysozyme, protease and alkaline phosphatase activity) and immune related gene expression (tumor necrosis factor α [tnfa], lysozyme [ly] and interleukin-1-beta, [il1b]) in the head-kidney were studied. The results revealed that feeding carp fry with 200 ml kg(-1) DPFE remarkably elevated the three skin mucus immune parameters tested (P < 0.05). However, evaluation of immune related gene expression demonstrated that the expression of tnfa and il1b was considerably decreased (P < 0.05) in fish fed DPFE diet, while the expression of ly remained similar (P > 0.05) compared to control fish (fed control diet). Furthermore, growth performance parameters were significantly improved in fry fed DPFE (P < 0.05). More studies are needed to understand different aspects of DPFE administration in fry mucosal immunity.

Interleukin-1 alpha variation is associated with the risk of developing preeclampsia.

OBJECTIVE: Preeclampsia is a syndrome that affects 5% of all pregnancies, producing substantial maternal and prenatal morbidity and mortality. Several studies have reported that cytokine genes are associated with the persistence of preeclampsia or the severity of the disease. The aim of this study is to investigate the relationships between the polymorphisms of interleukin-1 alpha-889 (IL-1A) gene and preeclampsia. METHOD: Genomic DNA was extracted from the peripheral blood of 305 patients with preeclampsia and 325 normal controls from Sayyad Shirazi Hospital of Golestan University. Then subjected to SSP-PCR amplification. STATA software and the chi square test were used for statistic calculations. RESULTS: The frequencies of IL-1A -889 genotypes C/C, T/T and C/T in preeclampsia cases were 34.8%, 8.2%, 57% and in controls were 20.9%, 7.6% and 71.3% respectively. There was a significant 1.5 fold excess frequency in genotype C/C in cases (CI=1.44-3.07, OR=2.1, P=0.0001). There was a significant difference in the frequencies of alleles or genotypes in IL-1A promoter regions between patients with preeclampsia and the control group. Turkomans showed the highest frequency of the C allele and Sistanies had the lowest frequency of the C allele in preeclampsia compared to control groups (CI=1.5-3.9, OR=2.48, P=0.0001). CONCLUSION: Our findings suggest that the IL-1A-899C/C genotype and C allele are associated with susceptibility to preeclampsia.

MicroRNA 17-92 expressed by a transposone-based vector changes expression level of cell-cycle-related genes.

The miR-17-92 cluster is composed of seven miRNAs (microRNAs; miR-17-5p, miR-17-3p, miR-18a, miR-19a, miR-20a, miR-19b-1 and miR-92a-1). Previous studies have indicated that this cluster is involved in cell proliferation and their overexpression has been seen in several types of cancer. We have assessed the overexpression effects of miR-17-92 on the expression of several genes associated with cell-cycle regulation. The human miR-17-92 gene was cloned into a transposone-based vector, piggyBac and transfected into HEK-293T [HEK-293 cells (human embryonic kidney cells) expressing the large T-antigen of SV40 (simian virus 40)] cell line. Gene expression analysis indicated that up-regulation of this cluster causes significant changes in the expression of several cell-cycle related genes, including CDK2 (cyclin-dependent kinase 2), cyclin-D2, c-Myc and CREB (cAMP-response-element-binding protein). Other methods of transcripts assessment confirmed miR-17-92 overexpression enhances cell proliferation.