Zivar Salehi

University of Guilan, Resht, Gīlān, Iran

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Publications (58)90.02 Total impact

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    ABSTRACT: In spite of variety studies in understanding of human reproductive and fertility, the underlying causes of male infertility remains undefined in about 50 % of cases. The polymorphism studies have a crucial role in diseases recognizing. Human apurinic/apyrimidinic endonuclease 1 (ApE1) is a multifunctional protein that has an important role in the base excision repair pathway. The present study was aimed to evaluate whether two polymorphisms -656T>G and 1349T>G ApE1 are related with the susceptibility to idiopathic male infertility. Samples were collected from 180 patients diagnosed with idiopathic male infertility and 120 control subjects and genotyped by tetra-primer amplification refractory mutation system PCR. We observed a significant difference in genotype distributions of -656T>G ApE1 polymorphism between infertile patients and controls (P = 0.0001). Our findings indicated individuals with the variant TG genotypes had a significant increased risk of idiopathic male infertility (OR 1.84, 95 % CI 1.09-3.11, P = 0.021), whereas the significant association between the 1349T>G polymorphism and idiopathic male infertility risk was not observed (P = 0.2). Our data suggest that the -656T>G ApE1 polymorphism may be associated with increased risk of idiopathic male infertility. Larger studies with more patients and controls are needed to confirm the results.
    International Urology and Nephrology 04/2015; DOI:10.1007/s11255-015-0979-z · 1.29 Impact Factor
  • Molecular Biology 01/2015; 49(1):168-170. DOI:10.1134/S0026893315010045 · 0.74 Impact Factor
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    ABSTRACT: Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and the leading cause of blindness in industrialized countries. Oxidative stress plays an important role in the development of microangiopathic complications in diabetes. Manganese superoxide dismutase (MnSOD) is a key mitochondrial antioxidant enzyme in the cellular defense against agents that induce oxidative stress. The aim of the present study was to assess whether the MnSOD A16V (C47T) polymorphism is associated with Diabetic retinopathy in northern Iran. 140 patients with Diabetic retinopathy and 140 healthy individuals, aged 30 to 75 years old, participated in this study. For genotyping of the MnSOD A16V polymorphism the polymerase chain reaction—restriction fragment length polymorphism (PCR-RFLP) method was used. The prevalence of genotype frequencies AA, AV, VV in Diabetic retinopathy subjects were 5.71, 71.43 and 22.86%, respectively, while in controls they were 21.43, 38.57 and 40%, respectively. A significantly increased frequency of the AV genotype was observed in patients as compared with controls (OR = 6.94, 95% CI = 2.98-16.20, P < 0.0001). In conclusion, it is suggested that the MnSOD A16V polymorphism may be associated with the risk of Diabetic retinopathy in northern Iran. However, larger population-based studies are needed for clarifying the relation between Diabetic retinopathy and the MnSOD A16V polymorphism.
    Molecular Biology 01/2015; 49(1):99-102. DOI:10.1134/S0026893315010057 · 0.74 Impact Factor
  • Molekuliarnaia biologiia 01/2015; 49(1):114-118. DOI:10.7868/S002689841501005X
  • Molekuliarnaia biologiia 01/2015; 49(1):190-192. DOI:10.7868/S0026898415010048
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    ABSTRACT: Development of gastric cancer (GC) is a multistep process that requires alterations in the expression of oncogenes and tumor suppressor genes, occurring over several decades. The p53 tumor suppressor protein is involved in cell-cycle control, apoptosis and DNA repair. One of the most important regulators of p53 is MDM2, which acts as a negative regulator in the p53 pathway. Based on the key role of p53 and MDM2 in tumor suppression, polymorphisms that cause change in their function might affect cancer risk. We therefore elevated associations of the polymorphisms of p53 (R72P) and MDM2 (SNP309) with GC in Iran.
    Asian Pacific journal of cancer prevention: APJCP 09/2014; 15(17):7413-7. DOI:10.7314/APJCP.2014.15.17.7413 · 1.50 Impact Factor
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    ABSTRACT: Endometriosis is defined as the presence of ectopic endometrial glands and stroma outside of the uterine cavity. Recent studies have shown that the oxidative stress causes irreparable damage, which leads to oxidative enzymopathies. Catalase gene encodes an antioxidant enzyme, detoxifying hydrogen peroxide to H2O and O2. The aim of this study was to determine whether the polymorphism at position -262 in the promoter region of catalase gene (C-262T), which alters the expression and enzyme blood levels, could have an impact on the risk of endometriosis. Extracted DNA from peripheral blood leucocytes was genotyped using allele-specific PCR (AS-PCR). The χ(2)-test was used for statistical analyses. In endometriosis subjects, the frequencies of the CAT CC/CT/TT were 67.5%, 32.5% and 0%, respectively, while in healthy women, they were 12%, 68% and 20%, respectively. Significant differences in allele and genotype distribution among controls and patients were found (OR, 178.76 95% CI, 10.11-3159.1202; p = 0.0004). This study indicates that catalase C-262T polymorphism is associated with the endometriosis. Randomised multicentre trials with greater sample sizes are still needed to clarify our results.
    Journal of Obstetrics and Gynaecology 08/2014; 35(3):1-3. DOI:10.3109/01443615.2014.948402 · 0.60 Impact Factor
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    ABSTRACT: Spontaneous abortion is the most common complication of early pregnancy. Genetic factors have been hypothesised to play a role in spontaneous abortion. Since it is possible that the balance of oxidants and antioxidants can be affected by different genetic variants, gene polymorphisms have been proposed as a susceptibility factor that increases the chance of abortion. Manganese superoxide dismutase is an important antioxidant enzyme encoded by manganese superoxide dismutase (MnSOD) gene. The aim of this experiment was to assess whether Val16Ala polymorphism of MnSOD gene is associated with abortion in north of Iran. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for genotyping. Statistical analyses were conducted using the χ(2)-test. The genetic distributions did not differ significantly between cases and controls, however slightly more Val/Val genotypes were found among the patients compared with control subjects (p = 0.059). No correlation was observed between susceptibility to abortion and MnSOD Val16Ala polymorphism. Larger population-based studies are needed for clarifying the relationship between abortion and MnSOD genotypes.
    Journal of Obstetrics and Gynaecology 08/2014; 35(2):1-4. DOI:10.3109/01443615.2014.937330 · 0.60 Impact Factor
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    ABSTRACT: Abstract About 10%-15% of conceptions are lost spontaneously prior to 20 weeks. Apart from the clinical problems, genetic variations have also been proposed as a susceptibility factor to miscarriage. Glutathione peroxidase 1 (GPX1) and catalase (CAT) encode two antioxidant enzymes that detoxify H2O2 and protect the cells from oxidative damage. A functional polymorphism at codon 198 of the GPX1 gene causes a C/T substitution in exon 2, which encodes for either proline or leucine (Pro198Leu). The CAT gene has a polymorphic site in the promoter region at position -262 (C-262T) which alters the expression and enzyme blood levels, leading to some pathological clinical conditions. In this study, we evaluated the association of these two polymorphisms with the risk of spontaneous abortion. Genomic DNA from 105 cases with spontaneous abortion and 90 healthy women were genotyped using allele-specific PCR (AS-PCR) and polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP). The genetic distributions for GPX1 did not differ significantly between cases and controls (p = 0.680). However, C-262T polymorphism was significantly associated with the risk of the disease (OR, 5.50; 95% CI, 1.43-21.09; p = 0.012). In conclusion, this study indicates that CAT -262T/T genotype confers less susceptibility to spontaneous abortion, while GPX1 Pro198Leu polymorphism may not be correlated with the disease.
    Systems Biology in Reproductive Medicine 07/2014; DOI:10.3109/19396368.2014.892651 · 1.70 Impact Factor
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    ABSTRACT: Implantation failure is a major limiting step for in-vitro fertilisation (IVF). Embryo implantation is the result of the interaction of the embryo with the endometrium. Oxidative stress (OS) can cause defective embryo development and retardation. Genetic polymorphisms of detoxicating enzymes, such as glutathione S-transferases (GSTs), may play an important role in the outcome of embryo implantation. GSTM1 and GSTT1 are known to be highly polymorphic. The aim of this study was to examine the association of GSTM1 and GSTT1 gene polymorphisms with IVF-ET outcome in a population in northern Iran. Blood samples were collected from 120 infertile women who underwent an IVF cycle, and 108 healthy volunteers. Genomic DNA was prepared from peripheral blood leucocytes. Genotype frequencies were determined in patients and healthy controls using polymerase chain reaction (PCR). It was found that 25.8% of the infertile women and 0% of the controls had the GSTM1 null genotype (odds ratio (OR) = 76.37; 95% CI = 4.6-1,265.7; p = 0.0025). On the other hand, 5% of the cases and 0% of the controls had the GSTT1 null genotype (OR = 12.3, 95% CI = 0.68-221/3, p = 0.088). These results suggest that GSTM1 null type might be associated with IVF outcome in a population in northern Iran.
    Journal of Obstetrics and Gynaecology 07/2014; DOI:10.3109/01443615.2014.930109 · 0.60 Impact Factor
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    ABSTRACT: Infertility is the failure of a couple to engender after endeavouring at least one full year of unprotected intercourse. It has been reported that reactive oxygen species contributed to pathogenesis of various disease. To inactivate ROS cells biosynthesise several antioxidant enzymes, one of them is catalase which contributes H2 O2 to H2 O and O2 . This study set out to delineate the association of catalase C-262T polymorphism with idiopathic male infertility. The study included 195 men with idiopathic infertility and 190 healthy volunteers. Genomic DNA was extracted from peripheral blood leucocytes. Genotype and allele frequencies were determined in patients and controls using allele-specific PCR (AS-PCR). The prevalence of genotype frequencies of the CAT CC/CT/TT was 31.79%, 65.12% and 3.07%, respectively, in infertile subjects, as against 24.73%, 55.26% and 20%, respectively, in healthy volunteers. Statistical analysis has emerged significant difference from the comparison of either genotype (P < 0.05). Taking into accounts of results, the catalase C-262T polymorphism indicates that CAT-262T/T genotype confers less susceptibility to male infertility. Further studies with larger numbers of patients are required for further evaluation and confirmation of our finding.
    Andrologia 01/2014; 47(1). DOI:10.1111/and.12228 · 1.17 Impact Factor
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    ABSTRACT: Hepatocyte growth factor (HGF), also known as scatter factor, and its receptor c-Met have been shown to be implicated in endometriosis. HGF acts as a mitogen, motogen, and morphogen on endometrial epithelial cells. The expression of c-Met on human endometrial cells has been reported. Many proteins are proteolytically released from the surface by a process known as ectodomain shedding. The aim of this study was to determine the levels of soluble c-Met (s-cMet) in the peritoneal fluid (PF) and serum samples of patients with different stages of endometriosis. 39 PF and serum samples from normal healthy and 130 samples from different stages of patients with endometriosis (33 cases of stage I, 38 stage II, 30 stage III and 29 stage IV) were included in this study. Total protein concentration (TPC) and the level of s-cMet in the PF and serum were determined by Bio-Rad protein assay based on the Bradford dye procedure and enzyme-linked immunosorbent assay, respectively. No significant change in the TPC was seen in the serum and PF of patients with endometriosis when compared with normal controls. Results obtained demonstrated that all PF and serum samples presented s-cMet expression, whereas, starting from stages I to IV endometriosis, a significant increase of s-cMet expression was observed as compared to controls. The results of this study show that a high expression of s-cMet is correlated with advanced stages of endometriosis. It is also concluded that the detection of serum and PF s-cMet may be useful in classifying endometriosis.
    Archives of Gynecology 11/2013; 289(5). DOI:10.1007/s00404-013-3082-7 · 1.28 Impact Factor
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    ABSTRACT: Endometriosis is a multifactorial gynecological condition characterized by the presence of ectopic endometrial and stromal tissue outside the uterus. Free radicals and Oxidative stress have been proposed to be involved in the pathogenesis of the endometriosis. It has been shown that mitochondrial DNA (mtDNA) is particularly susceptible to oxidative damage and mutations due to the high rate of reactive oxygen species production and limited DNA repair capacity in mitochondria. While a number of deletions can occur, the most commonly studied in human is a 4977-bp deletion that removes all or parts of the genes for NADH dehydrogenase subunits 3, 4, 4L and 5, cytochrome C oxidase subunit III and ATP synthase subunits 6 and 8.” We evaluated whether mtDNA common deletion is related with the susceptibility to endometriosis in northern Iran. In this study 80 endometriosis cases and 100 controls were enrolled. Total DNA was extracted from endometrial tissue samples. The mitochondrial common deletion was determined by Gap- polymerase chain reaction (Gap-PCR). It was found that the mitochondrial common deletion was more likely to be present in patients with endometriosis. Assessing indicate that 60 % of patients and 8 % of controls show mtDNA 4977-bp deletion (Odds Ratio [OR] = 17.25, P < 0.0001, confidence interval [CI] = 5.18–57.36). The mtDNA 4977 deletion may play a role in endometriosis. Further studies with larger numbers of patients are required for further evaluation and confirmation of our finding.
    Genes & genomics 10/2013; DOI:10.1007/s13258-013-0103-7 · 0.57 Impact Factor
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    ABSTRACT: Aims: MDM2 is a negative regulator of the p53, and has also been implicated in carcinogenesis. The aim of this study was to define the causal association of Helicobacter pylori infection and the MDM2 SNP309 among northern Iranian patients with gastric cancer (GC). Two hundred and eight patients with GC and 200 cancer-free controls were genotyped for MDM2 SNP309 using the polymerase chain reaction-restriction fragment length polymorphism method. The ureC (glmM) gene was used for detection of H. pylori in this study. Results: The G allele was found more frequently among patients with GC (55%) than among controls (37%). The risk of GC for MDM2 309G/G genotypes was considerably increased when compared with TT genotypes (odds ratio [OR]=15.93, 95% confidence interval [CI]=4.17-60.84). Among H. pylori-infected subjects, a significantly increased risk of GC associated with the GG genotype was quite clear (OR=14.66, 95% CI=3.54-60). Conclusions: The GG genotype was associated with an increased risk of gastric carcinoma. We also found that there is a joint effect of MDM2 SNP309G/G genotype and H. pylori infection for the development of gastric carcinoma. However, the findings need to be verified in large population-based prospective studies for more rigorous analyses of subgroups and gene-environment and gene-gene interactions.
    Genetic Testing and Molecular Biomarkers 09/2013; DOI:10.1089/gtmb.2013.0173 · 1.15 Impact Factor
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    Hajar Saber, Zivar Salehi, Saiedeh Sadri
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    ABSTRACT: Endometriosis is a chronic, inflammatory, estrogen dependent disease that affects up to 10% of all women of fertile age. It is characterized by the presence and proliferation of functional endometrial glands and stroma outside the uterine cavity. The aim of this study was to assess whether intron 4 (TTTA)n repeat and TCT deletion/insertion polymorphisms of CYP19 gene are associated with endometriosis in northern Iran. This study involved 110 patients with endometriosis and 200 healthy controls, who were genotyped for (TTTA) repeats in the fourth intron of the CYP19 gene. Genomic DNA from patients and controls was genotyped by polymerase chain reaction (PCR). A total of eight alleles were observed in our study population, ranging from 7 repeats to 13 repeats. (TTTA) repeat lengths of ⩽9 were classified as short (S), and those ⩾10 were classified as long (L). Compared to women who possessed the S/S genotype, those who carried L/L (OR, 5.56; 95% CI, 3.33–9.29) had significantly increased risk of endometriosis. There was a significant trend between L/L genotype and higher stage of endometriosis (P < 0.001). In conclusion, a significant association was identified between endometriosis and the CYP19 gene polymorphism, with endometriosis having longer CYP19 repeat lengths than control subjects. The strong association of CYP19 gene polymorphism with high-stage endometriosis suggests that CYP19 may have a prognostic implication.
    Egyptian Journal of Medical Human Genetics 04/2013; 14(2):165–169. DOI:10.1016/j.ejmhg.2012.10.002
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    ABSTRACT: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system that leads to loss of myelin and oligodendrocytes and damage to axons. Myelin oligodendrocyte glycoprotein (MOG) is a minor component of the myelin sheath, but is an important autoantigen linked to the pathogenesis of MS. Ciliary neurotrophic factor (CNTF) has been shown to enhance the generation, maturation, and survival of oligodendrocytes in culture medium. The aim of this study was to demonstrate the role of CNTF on MOG expression in the cerebral cortex of Cuprizone-induced MS mice. The mice were treated by Cuprizone for five weeks in order to induce MS. The mice were then divided into 3 groups. The first group was injected subcutaneously (SC) by CNTF in the amount of 250 μg/kg BW per day. The second group (SHAM) was injected SC by normal saline and the third group was left without injection as the control group. After four weeks the mice were killed and the cerebral cortex was harvested and the expression of MOG was studied by Western blotting. The data from this study show that the MOG expression was significantly increased in the CNTF-injected group as compared to the other groups. It is concluded that CNTF increases the MOG expression and may be important in the pathophysiology of MS. It is also concluded that CNTF may play a role in the process of remyelination by inducing the MOG expression.
    Cellular and Molecular Neurobiology 02/2013; DOI:10.1007/s10571-013-9918-7 · 2.20 Impact Factor
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    ABSTRACT: BACKGROUND AND AIM: Reactive oxygen species (ROS) are byproducts of the cellular metabolism and have important roles in normal physiology of the cell. However, when ROS production exceeds the antioxidant capacity, a state known as oxidative stress, damage to cellular macromolecules emerges. A crucial role in counteracting ROS is played by the enzyme catalase. A common polymorphism in the catalase (CAT) promoter region (C-262T) alters the expression as well as blood catalase levels, and leads to a number of human diseases. Ulcerative colitis (UC) is an inflammatory condition of the large bowel which is known to be influenced by oxidative stress. In this study, we aimed to evaluate the association of CAT C-262T polymorphism on the risk of UC. METHODS: Samples were collected from 60 patients diagnosed with UC and 78 control subjects, and genotyped by allele-specific PCR (AS-PCR). RESULTS: We found that CAT C-262T genotype frequencies were significantly different between cases and controls (p=0.002). Individuals carrying the -262C/T genotype had a greater risk for UC compared to C/C genotype (OR, 4.88; 95% CI, 1.73-13.75, p=0.002). CONCLUSIONS: This study indicates that CAT C-262T polymorphism may be associated with UC and the -262C/T genotype may be a risk factor for the disease. Further studies are needed to confirm the results.
    Journal of Gastroenterology and Hepatology 02/2013; 28(5). DOI:10.1111/jgh.12141 · 3.63 Impact Factor
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    ABSTRACT: Varicocele is the abnormal inflexion and distension of veins of the pampiniform plexus within spermatic cord and is one of the amendable causes of male infertility. It can increase reactive oxygen species (ROS) production in semen and cause oxidative stress. The purpose of this study was to analyse spermatozoa mtDNA 4977-bp deletion in infertile men with varicocele. To detect 4977-bp deletion in spermatozoa mtDNA, semen samples of 60 infertile patients with clinical varicocele and 90 normal men from northern Iran were prepared. After extraction of spermatozoa total DNA, Gap polymerase chain reaction (Gap PCR) was performed. 4977-bp deletion was observed in 81.66% of patients with varicocele, while approximately 15.55% of controls had this deletion. As spermatozoa from patients with varicocele had a high frequency of occurrence of 4977-bp deletion in mtDNA [OR = 24.18, 95% confidence interval (CI) = 10.15-57.57, P < 0.0001], varicocele may induce mtDNA deletion in spermatozoa and cause infertility in north Iranian men. However, to determine the relation between sperm mtDNA 4977-bp deletion and varicocele-induced infertility, larger population-based studies are needed. It is concluded that there is an association between sperm mtDNA 4977-bp deletion and varicocele-induced infertility in the population studied.
    Andrologia 02/2013; 46(3). DOI:10.1111/and.12073 · 1.17 Impact Factor
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    Zivar Salehi, Mahvash Hadavi
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    ABSTRACT: The TP53 gene is one of the most important tumor suppressor genes controlling DNA transcription and cell regulation. Common polymorphisms in p53 gene may play a role in some cancers. Some studies have reported an association between human papillomavirus (HPV) infections and prostate cancer. The aim of this study was to investigate whether the TP53 codon 72 polymorphism and HPV infection are responsible for susceptibility to prostate cancer in Iranian men. The prostate biopsies were taken during surgery from 68 Iranian prostatic cancer patients, and 85 patients with benign prostate hyperplasia. For genotyping of the p53 polymorphism at codon 72, PCRRFLP methods were used and the PCR products were digested with BstU1. An attempt was also made to detect HPV DNA in benign prostate hyperplasia and prostate cancer specimens. Among cancer cases, the distribution of Arg/Arg, Arg/Pro and Pro/Pro genotypes were 26.5%, 45.4%, and 19.1%, respectively. Among patients with benign prostate hyperplasia, the distribution of Arg/Arg, Arg/Pro, and Pro/Pro genotypes were 27%, 53%, and 20%, respectively. The allele frequencies did not differ significantly between prostate cancer and benign prostate hyperplasia samples. Human papillomavirus was detected only in three patients (4.4%; P = 0.71). The results from this study suggest that the TP53 codon 72 polymorphism and HPV infection do not confer susceptibility to prostate cancer in the Iranian population. Larger population-based studies are needed to clarify the relation between prostate carcinoma and p53 polymorphism and HPV infection.
    Journal of Medical Virology 09/2012; 84(9):1423-7. DOI:10.1002/jmv.23268 · 2.22 Impact Factor