فهرست مطالب

  • Volume:1 Issue:2, 2015
  • تاریخ انتشار: 1394/05/23
  • تعداد عناوین: 7
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  • Sareh Raeiszadeh Jahromi, Mahdi Bijanzadeh, Mahesh P. A, Sangeetha Vishweswaraiah, Nallur B. Ramachandra Pages 63-75
    Background
    Asthma is the main reason of disability, health resource exploitation and low quality of life for those who are affected. It is estimated that nearly 300 million people in the world are suffering from asthma. Studies have identified 18 genomic regions and more than 100 genes associated with asthma. Among these candidate genes, IL-17F plays a very interesting role in asthma. This study was conducted to predict the conformational and functional impact of asthma-associated IL-17F polymorphisms on protein product of the corresponding gene using Phyre2, PolyPhen2 and SIFT softwares.
    Methods
    In the present study, 10 significant missense SNPs (rs763780, rs144576902, rs11465553, rs368500268, rs141798304, rs2397084, rs146083682, rs200163061, rs376671742, and rs373228601) were taken from Ensembl Genome Browser database. Polymorphism-induced protein structural changes were predicted using Protein Homology analogY Recognition Engine V2.0 (PHYRE2) program. The possible impact of an amino acid substitution on the function of protein was analyzed using PolyPhen-2 (Polymorphism Phenotyping Version2) and SIFT (Sorting Intolerant From Tolerant) tools.
    Results
    The analysis revealed mutant proteins having structural changes in the number of atoms, H-bonds, turns and helices. While wild copy has 82 H-bonds, 5 helices and 20 turns, the mutant types show considerable changes. At functional level also, substantial changes were observed between the wild protein and the mutant one.
    Conclusion
    A single nucleotide polymorphism in the gene sequence can lead to the substantial structural and functional variations in the protein product of the gene, a process that may account for etiology of a number of complex diseases including asthma.
    Keywords: Asthma, SNP, IL-17F, Phyre2, PolyPhen2
  • Saghar Yousefnia Pages 77-88
    Background
    Cells have complex network of antioxidant enzymes that protect cells from induced damages by reactive oxygen species (ROS). Catalase and superoxide dismutase are known for their role as primary protection against oxidative stress. Oxidative damage is an important risk factor in age-related macular degeneration disease (AMD). For the first time in this study the impact of genetic polymorphisms of SOD1 and CAT with AMD has been examined. Hence, the association between genetic polymorphisms of catalase (CAT) C-262T, Cu/Zn superoxide dismutase (SOD1) A251G and risk of exudative AMD has been investigated.
    Methods
    This study was carried out on blood samples collected from 112 exudative AMD patients and 112 healthy individuals. Genotyping of CAT C-262T and SOD1A251G was done by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Differences in the frequencies were estimated using the χ2 test and risk was estimated with a logistic regression after adjusting for smoking, working place and age status.
    Results
    There was significant difference between CAT CT genotype and AMD disease (P=0.009, OR=0.38, 95%CI=0.18-0.78). Also T-allele has a significant association with risk of AMD and decreases risk of disease (P=0.036, OR=0.59, 95%CI=0.36-0.96), but there was no significant differences between SOD1A251G and variant homozygous and heterozygous frequencies in patients compared to controls (P=0.589, OR=0.77, 95%CI=0.3-1.96).
    Conclusions
    The data presented suggest that the T-allele in CAT genotypes can increase catalase expression and activity, as a result of which generation of reactive oxygen species (ROS) can be decreased. Therefore it is suggested that increased expression of CAT as a result of T-allele in CAT genotypes and existence of T-allele in CAT genotypes is associated with decreased risk of AMD.
    Keywords: Age-related macular degeneration (AMD), Catalase (CAT), Cu, Zn Superoxide dismutase (SOD1), Polymorphism
  • Mortaza Bonyadi, Elahe Nabat, Mahnaz Sadeghi Shabestari, Mandana Rafeey, Fakhrossadat Mortazavi Pages 89-94
    Background
    Henoch-Schönlein purpura (HSP) is an lgA mediated small vessel systemic vasculitis disease in children. The etiology and pathogenesis of HSP disease remain unknown. However, environmental and genetic risk factors could play important roles in susceptibility to HSP disease. In this study we investigated the association of 5՛-untranslated region polymorphism (-634G/C) of VEGF gene with HSP among Iranian Azeri Turkish population.
    Methods
    Thirty unrelated Iranian Azeri Turkish children with HSP and fifty healthy unrelated subjects without HSP and other inflammatory diseases were enrolled in this population. -634G/C polymorphism of VEGF gene was genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) technique.
    Results
    The distribution of CC genotype in VEGF -634G/C polymorphism statistically showed a significant difference in HSP patients in compare to that of control group (P= 0.009).
    Conclusions
    The CC genotype of VEGF -634G/C polymorphism could be associated with susceptibility to HSP disease in Iranian Azeri Turkish ethnic group.
    Keywords: 634G, C polymorphism, vascular endothelial growth factor (VEGF), Henoch, Schönlein purpura (HSP), Iran
  • Hamid Ali Bahar, Maysam Mard Soltani, Seyed Kazem Bidoki, Roomina Afzalzadeh Pages 95-103
    Background
    The impact of angiotensin converting enzyme (ACE) gene Insertion/deletion (I/D) polymorphism on etiology of type 2 of diabetes mellitus (T2DM) is well established. Reports show that unlike the II or T2DM genotypes the DD genotype of ACE is correlated with high risk of T2DM.In the present study the relationship between ACE gene polymorphism with the T2DM pathogenesis has been investigated in a population living in Khuzestan Province, Iran.
    Methods
    This case-control study performed on diabetic patients in Ahvaz Province, 99 cases and 100 normal individuals were enrolled in this study. T2DM patients were selected according to the WHO criteria. Blood sample was collected from each patient; DNA was extracted and subjected to PCR amplification using specific primers to identify different ACE genotypes (II, ID and DD).
    Results
    The chi-square analysis showed that lower frequency of DD genotype in patients is associated with increased risk of T2DM (Odds ratio= 0.273, P=0.004). However in patients suffering from T2DM the ID and II genotypes were significantly increased.
    Conclusions
    It appears that in T2DM a decrease in DD genotype of ACE and increases in DI and II genotypes is associated with changes in fasting blood sugar, triglyceride, total cholesterol; and blood pressure. These data may suggest that the DD genotype of ACE is associated with T2DM in Khuzestan Province.
    Keywords: Angiotensin Converting Enzyme, Polymorphism, Genetics Insertion, Deletion (I, D), Type 2 diabetes mellitus
  • Karim Mahnam, Azadeh Hoghoughi Pages 105-122
    Background
    New drugs namely; cladribine and fingolimodare known to be effective in treatment of multiple sclerosis (MS). The interaction of these drugs with the promoter region of the p53 gene may alter p53role in cancer progression. The aim of this study was to known the interaction of these compounds with p53 gene.
    Methods
    Binding free energy of the cladribine, fingolimod and their modified drugs for the p53 gene promoter were investigated using docking, 100 ns molecular dynamics simulations and MM/PBSA calculation.
    Results
    The results showed that both cladribine and modified cladribine (replacing -OH on carbon 3´ ribose sugar with -CH3 group) can bind the minor groove of p53 promoter, and inhibit the binding of transcription factors and expression of p53. However, fingolimodand its derivatives showed relatively weaker interaction with p53 promoter
    Conclusions
    Based on in silico studies we showed that the binding of cladribine to the p53 gene is stronger than that of fingolimod, hence it seems that the former drug can pose potential carcinogenic effects. The binding power and carcinogenic effect of sm-fingolimod (removing four carbons from its aliphatic tail) is more than that of fm-fingolimod (removing one carbon from its aliphatic tail).
    Keywords: Cladribine, Fingolimod, Molecular dynamics simulation, MM, PBSA, p53 gene
  • Safoura Khajeniazi Khajeniazi, Maryam Shahrabi Farahani, Masoud Soleimani Pages 123-133
    Background
    In recent years we have successfully adopted an in vitro hepatogenic differentiation of mesenchymal stem cells (MSCs). In this protocol the biologically active hepatocyte-like cells were differentiated from the stem cells isolated from either bone marrow or umbilical cord blood (UCB) samples. The aim of the present study was to compare the efficiency of the hepatogenic differentiation of MSCs isolated from UCB and MSCs.
    Methods
    Differentiation process of MSCs was carried out in a selective medium supporting hepatogenic differentiation for 3 weeks. Then using specific markers we have examined the hepatocyte formation following hepatogenic differentiation of the stem cells. Hepatogenic markers namely albumin, α-fetoprotein (AFP) and cytochrome P450 3A4 (CYP3A4) were monitored at different time intervals during differentiation.
    Results
    Transdifferentiation of the UCB and bone marrow MSCs was also characterized by measuring albumin, AFP and CYP3A4 at mRNA levels using reverse transcription polymerase chain reaction (RT-PCR). AFP was expressed in the undifferentiated UCB-MSCs and increased on day 21 of differentiation. However, AFP was not detected in the undifferentiated bone marrow MSCs. But, AFP expression started during the first week of differentiation. Albumin expression was detected in hepatocytes from UCB as well as bone marrow. The expression of albumin and its secretion from hepatocyte prepared from bone marrow appeared earlier compared to the cells derived from UCB. Metabolic function of the hepatocytes evaluated by secretion of albumin in the culture media was also similar in the cells isolated from both the sources.
    Conclusions
    The differentiation potential of MSCs derived from human UCB and bone marrow under in vitro condition is comparable. However, it appears that there is time-dependent difference in the onset of expression of liver specific markers particularly albumin synthesis in hepatocytes derived from different stem cells.
    Keywords: Stem cells, Hepatocyte, Differentiation, Umbilical cord blood, Bone marrow, Albumin
  • Somayeh Khatami, Ali Mohammad Ahadi, Hoda Ayat, Fereshteh Mardanian Pages 135-142
    Background
    Miscarriage is one of the most common pregnancy complications for which various causes have been defined, such as genetic factors, infectious, metabolic, endocrine systemmal function and immune system undesired responses. The early development of embryo occurs in oviduct and uterine tube from which some factors such as growth factors, glyco-proteins and factors those stimulate development of embryo are secreted. The ETF3 embryotrophic factor which is a complex of C3 complements and its derivatives i.e., iC3b, enhances the development of trophectodermas a consequence of which expression of relevant genes are affected embryo. There are various response elements in C3 gene promoter region such as, estrogen response regions (ERE). Steroids such as estrogen and progesterone are secreted in early steps of embryonic period along with C3 secretion and cause increase in C3 expression through interaction with regulatory elements in promoter region of this gene. In this study the polymorphism in ERE regions of C3 gene promoter was investigated in women suffering from recurrent miscarriage.
    Materials And Methods
    In this study, assuming that polymorphism in ERE regions is correlated with recurrent miscarriage during early months of pregnancy, 40 blood samples were collected from female patients admitted to an Infertility Clinic, Isfahan, Iran. DNA was extracted, amplification of regions harboring ERE with a pair of specific primer was done using Polymerase Chain Reaction-Single Strand Chain Polymorphism (PCR-SSCP) for studying possible polymorphisms in this region.
    Results and
    Conclusion
    The results indicated a specific symptomless infertility among the women, however there was no correlation between the ERE polymorphism and symptoms in control and cases.
    Keywords: Spontaneous, Recurrent Abortion, Complement 3, Estrogen Response Element