Silencing of α-N-acetylgalactosaminidase in the gastric cancer cells amplified cell death and attenuated migration, while the multidrug resistance remained unchanged.

Although the elevated level of the α-N-acetylgalactosaminidase enzyme (encoded by the NAGA gene) is a well-recognized feature of cancer cells; little research works have been undertaken on the cancer malignancy mechanisms. The effects of NAGA gene downregulation on cancer cells' features such as drug resistance, impaired programmed cell death, and migration were analyzed in this study. The cells grew exponentially with a doubling time of 30 h in an optimal condition. Toxicity of daunorubicin chemotherapy drug on NAGA-transfected EPG85.257RDB cells was evaluated in comparison to control cells and no significant change was recorded. Quantitative transcript analyses and protein levels revealed that the MDR1 pump almost remained unchanged during the study. Moreover, the NAGA gene downregulation enhanced the late apoptosis rate in EPG85.257RDB cells at 24 h posttransfection. The investigated expression level of genes and proteins involved in the TNFR2 signaling pathway, related to cancer cell apoptosis, showed considerable alterations after NAGA silencing as well. MAP3K14 and CASP3 genes were downregulated while IL6, RELA, and TRAF2 experienced an upregulation. Also, NAGA silencing generally diminished the migration ability of EPG85.257RDB cells and the MMP1 gene (as a critical gene in metastasis) expression decreased significantly. The expression of the p-FAK protein, which is located in the downstream of the α2 ß1 integrin signaling pathway, was reduced likewise. It could be concluded that despite drug resistance, NAGA silencing resulted in augmentative and regressive effects on cell death and migration.

Novel MYO15A variants are associated with hearing loss in the two Iranian pedigrees.

BACKGROUND: Clinical genetic diagnosis of non-syndromic hearing loss (NSHL) is quite challenging. With regard to its high heterogeneity as well as large size of some genes, it is also really difficult to detect causative mutations using traditional approaches. One of the recent technologies called whole-exome sequencing (WES) has been thus developed in this domain to remove the limitations of conventional methods. METHODS: This study was a report on a research study of two unrelated pedigrees with multiple affected cases of hearing loss (HL). Accordingly, clinical evaluations and genetic analysis were performed in both families. RESULTS: The results of WES data analysis to uncover autosomal recessive non-syndromic hearing loss (ARNSHL) disease-causing variants was reported in the present study. Initial analysis identified two novel variants of MYO15A i.e. c.T6442A:p.W2148R and c.10504dupT:p.C3502Lfs*15 correspondingly which were later confirmed by Sanger validations and segregation analyses. According to online prediction tools, both identified variants seemed to have damaging effects. CONCLUSION: In this study, whole exome sequencing were used as a first approach strategy to identify the two novel variants in MYO15A in two Iranian families with ARNSHL.

In silico and in vitro effects of the I30T mutation on myelin protein zero instability in the cell membrane.

Charcot-Marie-Tooth (CMT) diseases are a heterogeneous group of genetic peripheral neuropathies caused by mutations in a variety of genes, which are involved in the development and maintenance of peripheral nerves. Myelin protein zero (MPZ) is expressed by Schwann cells, and MPZ mutations can lead to primarily demyelinating polyneuropathies including CMT type 1B. Different mutations demonstrate various forms of disease pathomechanisms, which may be beneficial in understanding the disease cellular pathology. Our molecular dynamics simulation study on the possible impacts of I30T mutation on the MPZ protein structure suggested a higher hydrophobicity and thus lower stability in the membranous structures. A study was also conducted to predict native/mutant MPZ interactions. To validate the results of the simulation study, the native and mutant forms of the MPZ protein were separately expressed in a cellular model, and the protein trafficking was chased down in a time course pattern. In vitro studies provided more evidence on the instability of the MPZ protein due to the mutation. In this study, qualitative and quantitative approaches were adopted to confirm the instability of mutant MPZ in cellular membranes.

A Novel Cadherin 23 Variant for Hereditary Hearing Loss Reveals Additional Support for a DFNB12 Nonsyndromic Phenotype of CDH23.

BACKGROUND AND OBJECTIVES: Identification of the pathogenic mutations underlying hereditary hearing loss (HL) is difficult, since causative mutations in 60 different genes have so far been reported. METHODS: A comprehensive clinical and pedigree examination was performed on a multiplex family suffering from HL. Direct sequencing of GJB2 and genetic linkage analysis of 5 other most common recessive nonsyndromic HL (ARNSHL) genes were accomplished. Next-generation sequencing (NGS) was utilized to reveal the possible genetic etiology of the disease. RESULTS: NGS results showed a novel rare variant c.2977G>A (p.Asp993Asn) in the CDH23 gene. The variant, which is a missense in exon 26 of the CDH23 gene, fulfills the criteria of being categorized as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guideline. Electroretinography rejects the Usher syndrome in the family. CONCLUSIONS: The present study shows that an accurate molecular diagnosis based on NGS technologies largely improves molecular-diagnostic outcome and thus genetic counseling, and helps to clarify the recurrence risk in deaf families.

Differentiation of dental pulp stem cells into neuron-like cells.

Background and objectives: With regard to their ease of harvest and common developmental origin, dental pulp stem cells (DPSCs) may act as a favorable source of stem cells in generation of nerves. Moreover; cellular migration and differentiation as well as survival, self-renewal, and proliferation of neuroprogenitor species require the presence of the central nervous system (CNS) mitogens including EGF and bFGF. Accordingly, the possibility of the induction of neuronal differentiation of DPSCs by EGF and bFGF was evaluated in the present study.Materials and methods: DPSCs were treated with 20 ng/ml EGF, 20 ng/ml bFGF, and 10 µg/ml heparin. In order to further induce the neuroprogenitor differentiation, DPSC-derived spheres were also incubated in serum-free media for three days. The resulting spheres were then cultured in high-glucose Dulbecco's Modified Eagle Medium (DMEM) with 10% FBS. The morphology of the cells and the expression of the differentiation markers were correspondingly analyzed by quantitative polymerase chain reaction (qPCR), western blotting, and immunofluorescence (IF).Results: The EGF/bFGF-treated DPSCs showed significant increase in the expression of the neuroprogenitor markers of Nestin and SRY (sex determining region Y)-box 2 (SOX2), 72 h after treatment. The up-regulation of Nestin and SOX2 induced by growth factors was confirmed using western blotting and IF. The cultures also yielded some neuron-like cells with a significant rise in Nestin, microtubule-associated protein 2 (MAP2), and Neurogenin 1 (Ngn1) transcript levels; compared with cells maintained in the control media (p < 0.05).Conclusion: DPSCs seemed to potentially differentiate into neuron-like cells under the herein-mentioned treatment conditions.

A novel pathogenic variant in the MARVELD2 gene causes autosomal recessive non-syndromic hearing loss in an Iranian family.

BACKGROUND AND AIMS: Hearing loss (HL) is the most common sensorineural disorder and one of the most common human defects. HL can be classified according to main criteria, including: the site (conductive, sensorineural and mixed), onset (pre-lingual and post-lingual), accompanying signs and symptoms (syndromic and non-syndromic), severity (mild, moderate, severe and profound) and mode of inheritance (Autosomal recessive, autosomal dominant, X-linked and mitochondrial). Autosomal recessive non-syndromic HL (ARNSHL) forms constitute a major share of the HL cases. In the present study, next-generation sequencing (NGS) was applied to investigate the underlying etiology of HL in a multiplex ARNSHL family from Khuzestan province, southwest Iran. METHODS: In this descriptive study, 20 multiplex ARNSHL families from Khuzestan province, southwest of Iran were recruited. After DNA extraction, genetic linkage analysis (GLA) was applied to screen for a panel of more prevalent loci. One family, which was not linked to these loci, was subjected to Otogenetics deafness Next Generation Sequencing (NGS) panel. RESULTS: NGS results showed a novel deletion-insertion variant (c.1555delinsAA) in the MARVELD2 gene. The variant which is a frameshift in the seventh exon of the MARVELD2 gene fulfills the criteria of being categorized as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guideline. CONCLUSION: NGS is very promising to identify the molecular etiology of highly heterogeneous diseases such as HL. MARVELD2 might be important in the etiology of HL in this region of Iran.

Update of spectrum c.35delG and c.-23+1G>A mutations on the GJB2 gene in individuals with autosomal recessive nonsyndromic hearing loss.

Hearing loss (HL) is the most common birth defect and the most prevalent sensorineural condition worldwide. It is associated with more than 1,000 mutations in at least 90 genes. Mutations of the gap junction beta-2 protein (GJB2) gene located in the nonsyndromic hearing loss and deafness (DFNB1) locus (chromosome 13q11-12) are the main causes of autosomal recessive nonsyndromic hearing loss worldwide, but important differences exist between various populations. In the present article, two common mutations of the GJB2 gene are compared for ethnic-specific allele frequency, their function, and their contribution to genetic HL in different populations. The results indicated that mutations of the GJB2 gene could have arisen during human migration. Updates on the spectrum of mutations clearly show that frequent mutations in the GJB2 gene are consistent with the founder mutation hypothesis.

A Novel Pathogenic Variant in the CABP2 Gene Causes Severe Nonsyndromic Hearing Loss in a Consanguineous Iranian Family.

BACKGROUND AND OBJECTIVES: Hereditary hearing loss (HL) can originate from mutations in one of many genes involved in the complex process of hearing. CABP2 mutations have been reported to cause moderate HL. Here, we report the whole exome sequencing (WES) of a proband presenting with prelingual, severe HL in an Iranian family. METHODS: A comprehensive family history was obtained, and clinical evaluations and pedigree analysis were performed in the family with 2 affected members. After excluding mutations in the GJB2 gene and 7 other most common autosomal recessive nonsyndromic HL (ARNSHL) genes via Sanger sequencing and genetic linkage analysis in the family, WES was utilized to find the possible etiology of the disease. RESULTS: WES results showed a novel rare variant (c.311G>A) in the CABP2gene.This missense variant in the exon 4 of the CABP2gene meets the criteria of being pathogenic according to the American College of Medical Genetics and Genomics (ACMG) interpretation guidelines. CONCLUSIONS: Up to now, 3 mutations have been reported for the CABP2gene to cause moderate ARNSHL in different populations. Our results show that CABP2variantsalso cause severe ARNSHL, adding CABP2to the growing list of genes that exhibit phenotypic heterogeneity. Expanding our understanding of the mutational spectrum of HL genes is an important step in providing the correct clinical molecular interpretation and diagnosis for patients.

Identification and Clinical Implications of a Novel MYO15A Variant in a Consanguineous Iranian Family by Targeted Exome Sequencing.

BACKGROUND AND OBJECTIVES: Hereditary hearing loss (HL) is known by a very high genetic heterogeneity, which makes a molecular diagnosis problematic. Next-generation sequencing (NGS) is a new strategy that can overcome this problem. METHOD: A comprehensive family history was obtained, and clinical evaluations and pedigree analysis were performed in the family with 3 affected members. After excluding mutations in the GJB2 and 7 other most common autosomal recessive nonsyndromic HL genes via Sanger sequencing and genetic linkage analysis in the family, we applied the Otogenetics deafness NGS panel in the proband of this family. RESULTS: NGS results showed a novel rare variant (c.7720C>T) in the MYO15A gene. This nonsense variant in the exon 40 of the MYO15A gene fulfills the criteria of being categorized as pathogenic according to the American College of Medical Genetics and Genomics guideline. CONCLUSIONS: New DNA sequencing technologies could lead to identification of the disease causing variants in highly heterogeneous disorders such as HL.

A pathogenic variant in SLC26A4 is associated with Pendred syndrome in a consanguineous Iranian family.

Objective: Hearing loss (HL) is a common sensory deficit with high phenotypic and genotypic heterogeneity. A large Iranian family with HL was genetically assessed in this study. Design: A proband from a consanguineous multiplex HL family from Iran was examined via Targeted Next-Generation Sequencing (TNGS). Sanger sequencing allowed the segregation analysis of the variant of interest and the investigation of its presence in a cohort of 50 ethnicity-matched healthy control individuals. The gene was previously associated with HL. Therefore, to determine whether the variant was specifically associated with Pendred Syndrome (PDS) or DFNB4, biochemical analyses, PTA, thyroid scans by Tc99m, perchlorate discharge test and high-resolution CT scan of the temporal bone were carried out on the affected family members. Study sample: Ten members of a large multiplex Iranian family with HL were recruited in this study. In addition, 50 unrelated healthy controls of the same ethnic group were randomly selected to genotype the variant. Results: A homozygous missense variant (NM_000441.1: c.1211C > T/p.Thr404Ile) in exon 10 was found segregating in the family. Based on the ACMG's guidelines, the variant was classified as pathogenic. Conclusion: This study expands the spectrum of SLC26A4 pathogenic variants in hearing loss.

A novel variant of SLC26A4 and first report of the c.716T>A variant in Iranian pedigrees with non-syndromic sensorineural hearing loss.

The autosomal recessive non-syndromic hearing loss (ARNSHL) can be associated with variants in solute carrier family 26, member 4 (SLC26A4) gene and is the second most common cause of ARNSHL worldwide. Therefore, this study aims to determine the contribution of the SLC26A4 genotype in the hearing loss (HL) of 40 ARNSHL pedigrees in Iran. A cohort of the 40 Iranian pedigrees with ARNSHL, having no mutation in the GJB2 gene, was selected. The linkage analysis with five short tandem repeat (STR) markers linked to SLC26A4 was performed for the 40 ARNSHL pedigrees. Then, two out of the 40 pedigrees with ARNSHL that linked to DFNB4 locus were further screened to determine the variants in all exons of SLC26A4 gene by direct DNA sequencing. The 21 exons of SCL26A4 were analyzed for the two pedigrees. A known variant (c.716T>A homozygote), it is the first reported incidence in Iran, a novel variant (c.493A>C homozygote) were detected in the two pedigrees and pathogenesis of c.493A>C confirmed in this study with review 100 hearing ethnically matched controls by PCR-RFLP analysis. The present study suggests that the SLC26A4 gene plays a crucial role in the HL occurring in Iranian pedigrees. Also, the results probably support the specificity and unique spectrum of SLC26A4 variants among Iranian HL patients. Molecular study of SLC26A4 gene may lead to elucidation of the profile of the population-specific variants which has importance in diagnostics of HL.

cag Pathogenicity island-dependent upregulation of matrix metalloproteinase-7 in infected patients with Helicobacter pylori.

Helicobacter pylori (H. pylori) infection has been involved in the pathogenesis of most important gastroduodenal diseases. Matrix metalloproteinases (MMPs) are a large family of zincendopeptidases which play important roles in degradation of extracellular matrix (ECM) and various inflammatory diseases. Therefore, we examined MMP-7 mRNA levels in the gastric mucosa of patients with H. pylori infection and evaluated the effects of virulence factors, such as vacA (vacuolating cytotoxin A) and cagA (cytotoxin-associated gene), in H. pylori-infected patients upon the MMP-7 mRNA mucosal levels. We also determined the correlation between mucosal MMP-7 mRNA levels and the types of disease. Total RNA was extracted from gastric biopsies of 50 H. pylori-infected patients and 50 uninfected individuals. Mucosal MMP-7 mRNA expression level in H. pylori-infected and non-infected gastric biopsies was determined by real-time polymerase chain reaction (PCR). The presences of cagA and vacA virulence factors was evaluated using PCR. MMP-7 expression was significantly higher in biopsies of patients infected with H .pylori compared to uninfected individuals. In addition, mucosal MMP-7 mRNA expression in H. pylori-infected patients significantly associated with the cagA status and the types of disease. Our results suggest that MMP-7 might be involved in the pathogenesis of H. pylori. Peptic ulcer was associated with cag pathogenicity island-dependent MMP-7 upregulation.

MicroRNAs: effective elements in ear-related diseases and hearing loss.

miRNAs are important factors for post-transcriptional process that controls gene expression at mRNA level. Various biological processes, including growth and differentiation, are regulated by miRNAs. miRNAs have been demonstrated to play an essential role in development and progression of hearing loss. Nowadays, miRNAs are known as critical factors involved in different physiological, biological, and pathological processes, such as gene expression, progressive sensorineural hearing loss, age-related hearing loss, noise-induced hearing loss, cholesteatoma, schwannomas, and inner ear inflammation. The miR-183 family (miR-183, miR-96 and miR-182) is expressed abundantly in some types of sensory cells in inner ear specially mechanosensory hair cells that exhibit a great expression level of this family. The plasma levels of miR-24-3p, miR-16-5p, miR-185-5p, and miR-451a were upregulated during noise exposures, and increased levels of miR-21 have been found in vestibular schwannomas and human cholesteatoma. In addition, upregulation of pro-apoptotic miRNAs and downregulation of miRNAs which promote differentiation and proliferation in age-related degeneration of the organ of Corti may potentially serve as a helpful biomarker for the early detection of age-related hearing loss. This knowledge represents miRNAs as promising diagnostic and therapeutic tools in the near future.

In Vitro Differentiation of Human Bone Marrow Mesenchymal Stem Cells to Hair Cells Using Growth Factors.

OBJECTIVE: In this study, we attempted to differentiated human bone marrow-derived mesenchymal stem cells (hBMSCs) to auditory hair cells using growth factors. METHODS: Retinoic acid (RA), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) were added to hBMSCs cell culture medium. The cells were evaluated morphologically and the expression of SOX2, POU4F3, MYO7A, and Calretinin at mRNA level and ATOH1 mRNA and protein expression. RESULTS: After treatment with the growth factors, the morphology of the cells did not change, but evaluation of gene expression at the mRNA level increased the expression of the ATOH1, SOX2, and POU4F3 markers. Growth factors increased the expression of ATOH1 at the protein level. The expression of calretinin showed decreased and MYO7A no significant change in expression. CONCLUSION: hBMSCs have the potential to differentiate to hair cell-like using the RA, bFGF, and EGF.

A Review of Medicinal Plants for the Treatment of Earache and Tinnitus in Iran.

BACKGROUND AND PURPOSE: Despite numerous trials, there has not yet been any definite strategy to reduce replicable long-term tinnitus and earache. Complementary and alternative medical approaches have been used to decrease the symptoms of tinnitus and earache. This study was conducted to report medicinal plants that are used to treat ear disorders, especially earache and tinnitus in different regions of Iran. EVIDENCE ACQUISITIONS: Directory of Open Access Journals (DOAJ), Google Scholar, PubMed, LISTA (EBSCO), Embase, and Web of Science were searched using relevant search terms to retrieve eligible publications. RESULTS: Twenty-three species from sixteen families were used for the treatment of earache and tinnitus in Iran. Plants from families Asteraceae and Lamiaceae were the most commonly used plants for the treatment of earache. Ginkgo biloba was frequently reported for the treatment of tinnitus. CONCLUSION: This study shows the important role of medicinal plants in the treatment of earache and tinnitus in some regions of Iran. The medicinal plants reported in this review can be considered in treatments for earache and tinnitus if examined more extensively in clinical trials.

Ginkgo biloba in the treatment of tinnitus: An updated literature review.

INTRODUCTION: Tinnitus is one of the common diseases of the ear that is associated with numerous physical and mental disorders. One of the known mechanisms in the tinnitus area with unknown reason is oxidative events. Based on the prevalence and economic costs and physical- psychological side effects caused by tinnitus and the importance of finding a suitable solution for its prevention and treatment, the need for further studies becomes more obvious in this context. This review article aimed to review studies on the effectiveness of Ginkgo biloba as a medicinal plant on patients with tinnitus. EVIDENCE ACQUISITIONS: Google Scholar, Directory of Open Access Journals (DOAJ), PubMed, LISTA (EBSCO) and Web of Science have been searched. RESULTS: There are many studies on the therapeutic effect of Ginkgo biloba on patients with tinnitus. Most findings are in contrast with each other so that some of studies reported that Ginkgo biloba is effective in the treatment of tinnitus and other studies referred to it as ineffective herbal medicine. Generally, according to the previous studies and the present study, it can mention that the Ginkgo biloba may somewhat improve tinnitus. CONCLUSION: Since tinnitus is multifactorial, it is recommended to evaluate patients individually based on the cause of tinnitus, treatment formulas, and different doses of Ginkgo biloba at the more extensive level in future studies.

Comparison of Three Types of Mesenchymal Stem Cells (Bone Marrow, Adipose Tissue, and Umbilical Cord-Derived) as Potential Sources for Inner Ear Regeneration.

In this review, we compared the potential of mesenchymal stem cells derived from bone marrow, adipose tissue and umbilical cord as suitable sources for regeneration of inner ear hair cells and auditory neurons. Our intensive literature search indicates that stem cells in some of adult mammalian tissues, such as bone marrow, can generate new cells under physiological and pathological conditions. Among various types of stem cells, bone marrow-derived mesenchymal stem cells are one of the most promising candidates for cell replacement therapy. Mesenchymal stem cells have been reported to invade the damaged area, contribute to the structural reorganization of the damaged cochlea and improve incomplete hearing recovery. We suggest that bone marrow-derived mesenchymal stem cells would be more beneficial than other mesenchymal stem cells.

Altered Th17 Cytokine Expression in Helicobacter pylori Patients with TLR4 (D299G) Polymorphism.

Helicobacter pylori (H. pylori) is associated with gastric ulcer and gastric adenocarcinoma. Polymorphisms in the host genes coding for Toll-like receptors (TLRs) may influence the innate and adaptive immune response to the infection, affecting the susceptibility to H. pylori or the disease outcomes. However, the details and association with different polymorphism and clinical expression of infection remain unclear. A case-control study consisting of 58 patients with H. pylori infection and 44 H. pylori uninfection was conducted. Genomic DNA was extracted and genotypes of TLR4 Asp299Gly polymorphism were assessed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Mucosal cytokines expression in H. pylori-infected and uninfected gastric biopsies was determined by real-time PCR. The expression of IL-6, IL-17, IL-21, IL-23 and TGF-ß1 was significantly higher in patients with D299G polymorphism in TLR4. But the expression of IL-18 between patients with single-nucleotide polymorphisms (SNPs) in TLR4 and patients with the wild-type allele was not significant. In H. pylori-infected patients with gastritis, SNPs in TLR4 may alter cytokine expression toward Th17 immune response in the gastric mucosa and may have increased risk for the development of peptic ulcer.

Frequency of virulence factors in Helicobacter pylori-infected patients with gastritis.

UNLABELLED: The outcome of Helicobacter pylori infection has been related to specific virulence-associated bacterial genotypes. The vacuolating cytotoxin (vacA), cagA gene, oipA and babA2 gene are important virulence factor involving gastric diseases. The objective of this study was to assess the relationship between virulence factors of H. pylori and histopathological findings. MATERIAL AND METHODS: Gastroduodenoscopy was performed in 436 dyspeptic patients. Antrum biopsy was obtained for detection of H. pylori, virulence factors and for histopathological assessment. The polymerase chain reaction was used to detect virulence factors of H. pylori using specific primers. RESULTS: vacA genotypes in patients infected with H. pylori were associated with cagA, iceA1 and iceA2. In the patients with H. pylori infection there was a significant relationship between cagA positivity and neutrophil activity (P = 0.004) and chronic inflammation (P = 0.013) and with H. pylori density (P = 0.034). Neutrophil infiltration was found to be more severe in the s1 group than in the s2 group (P = 0.042). Also was a significant relationship between oipA positivity and neutrophil activity (P = 0.004) and with H. pylori density (P = 0.018). No significant relationships were observed between other vacA genotypes and histopathological parameters. CONCLUSION: H. pylori strains showing cagA, vacA s1 and oipA positivity are associated with more severe gastritis in some histological features but virulence factors of H. pylori do not appear to determine the overall pattern of gastritis.

A preliminary study of inherited thrombophilic risk factors in different clinical manifestations of venous thromboembolism in central Iran.

BACKGROUND & OBJECTIVES: Inherited thrombophilia is known to be an important risk factor for developing venous thromboembolism. Whether such abnormalities may impact the development of deep vein thrombosis (DVT) and pulmonary embolism (PE) differently is not well defined. This preliminary study was undertaken to compare thrombophilic polymorphism in patients with DVT and PE. METHODS: A total of 35 DVT, 23 DVT/PE, and 37 PE patients admitted to the Hajar Hospital, Shahrekord, Iran, between October 2009 and February 2011 were included in the study and 306 healthy volunteers matched by age and sex from the same geographical area with no history of venous or arterial diseases were included as control group. Factor V Leiden (FV 1691G/A, rs6025), prothrombin (FII 20210G/A), methylene tetrahydrofulate reductase (MTHFR 677C/T, rs1801133), and PLA2 polymorphisms of platelet glycoprotein IIb/IIIa (GpIIIa 1565T/C, rs5918) were investigated by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The number of patients with the investigated polymorphisms and homozygous carriers was significantly different among the groups (P<0.05). No significant difference was observed in the presence of FV 1691G/A and FII 20210G/A between any of the patients groups and the control group. GpIIIa 1565T/C and homozygous MTHFR 677C/T polymorphisms were higher in DVT patients compared with the control group (OR=6.65, 95% CI=3.09-14.30 and OR=4.08, 95% CI=1.35-12.38, respectively). INTERPRETATION & CONCLUSIONS: As none of the investigated polymorphisms were associated with PE, other thrombophilia polymorphisms may have a role in the pathogenesis of PE in these patients and should be investigated. Because of different prognostic risk factors among different types of patients, the treatment approach could be different.