Tehran University Medical Journal

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Our understanding of the pathogenesis of endocrine disorders increase rapidly by genetic studies at the molecular level. Common endocrine disorders such as diabetes mellitus, obesity, osteoporosis, dyslipidemia and cancer follow the multifactorial model in the genetic aspect. This review tries to clarify the approach in molecular studies of such diseases for clinicians in different specialties. How to evaluate a possible association between a single nucleotide polymorphism and an endocrinopathy or its complication is the main concern of this review. Two approaches for gene mapping will be discussed as well as main challenges regarding each approach. All such genetic studies ideally include some test of the association between genome sequence variation and the phenotype of interest such as the trait itself, the presence of a given complication, or measures of some endocrinopathy-related intermediate trait. Despite different advances in this analysis, there are major concerns regarding the overall performance and robustness of genetic association studies. By using powerful new high-throughput methods, further insights to molecular basis of such endocrine disorders can be expected. Close correlation between geneticists and clinicians can effectively bridge between basic sciences and clinical investigations.

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Background: There are several evidences that genetic factors besides environmental triggers have important role in initiating the rheumatoid arthritis (RA). The aim of this study was to investigate the association of rheumatoid arthritis with different subtypes of HLA DR4 in Iranian patients.

Methods: In an un-matched case control study, 110 rheumatoid arthritis patients (case) and 56 knee osteoarthritis patients (control) of outpatient clinic in Shariati Hospital were entered to the study. After blood sampling from case and control groups, DNA was isolated by using salting-out method and HLA DR4 and its subtypes were detected. Association of HLA DR4 and its subtypes with rheumatoid arthritis, rheumatic factor and clinical manifestations of diseases was evaluated.

Results: Eighty nine (80.9%) of rheumatoid arthritis patients were female and 21 were male. Thirty four of the RA patients (30.9%) and eleven subjects from the control group (19.6%) were HLA DR4 positive (p=0.12). The most frequent subtype of HLA DR4 in RA patients was 0404 and in control group was 0401 (p=0.03). There were not statistically significant association between HLA DR4 and age of disease onset, family history, morning stiffness and rheumatoid factor. Joint swelling and tenderness had association with HLA DR4 (p=0.04 and p=0.03).

Conclusion: Although there were no statistically significant association between rheumatoid arthritis and HLA DR4, but prevalence of this HLA was higher in patients than control. It is possible that in some ethnics, other HLAs may have role in pathogenesis of disease.

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Background: Pi-GST and Mu-GST are subclasses of glutathione S-transferase that present on human sperm surface and play an important role against oxidative stress. Therefore, any defects in the enzyme activity may be associated with male infertility.In this study the polymorphisms of GSTM1 and GSTP1 in association with enzyme activity and sperm parameters were studied.

Methods: This case-control study involved 95 men with oligoastenoteratozoospermia and 26 controls with normozoospermia. Semen analyses were carried out according to WHO guidelines. Blood DNA was extracted using salting out procedures. GSTM1 and GSTP1 polymorphisms gene were determined through PCR-RFLP and multiplex PCR, respectively. Finally, Glutathione S-transferase activity was measured.

Results: Frequencies of GSTM1 null genotype in oligoastenoteratospermic and normospermic groups were 52.1% and 53.8% respectively. There were no statistically significant differences in sperm parameters and enzyme activity between GSTM1 null and positive genotypes in two groups. There were no statistically significant differences in glutathione S-transferase activity between oligoastenoteratospermia and normospermic groups (p>0.05). All the 121 men in this study had Ile/Ile genotypes at 105 codon of GSTP1. Frequency of normal homozygote (114Ala/Ala), heterozygote (114Ala/Val) and mutant homozygote (114Val/Val) genotypes in oligoastenoteratospermic group were 81.1%, 17.9% and 1.1% respectively but in the control group they were 88.5%, 11.5% and null.

Conclusions: Total glutathione S-transferase activity and sperm parameters were not affected by deficient Glutathione S-transferase activity in GSTM1 null genotype. Compensate activity of other sperm surface glutathione S-transferase isozymes, like GSTP1, may justify the cause.

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The prostate is a small gland located below the bladder and upper part of the urethra. In developed countries prostate cancer is the second common cancer (after skin cancer), and also the second leading cause of cancer death (after lung cancer) among men. The several studies have been shown prostate cancer familial aggregation. The main reason for this aggregation is inheritance included genes. The family history is an important risk factor for developing the disease. The genes AR, CYP17, SRD5A2, HSD3B1 and HSD3B2 are all intimately involved in androgen metabolism and cell proliferation in the prostate. Each shows intraspecific polymorphism and variation among racial-ethnic groups that is associated with the risk of prostate cancer. Some of genes expressed in the prostate are in association with the production of seminal fluid and also with prostate cancer. Epigenetic modifications, specifically DNA hypermethylation, are believed to play an important role in the down-regulation of genes important for protection against prostate cancer. In prostate cancer numerous molecular and genetic aberrations have been described. It is now well established that cancer cells exhibit a number of genetic defects in apoptotic pathways. In this review article, the most recent data in molecular genetic, prevention and especially gene therapy in prostate cancer are introduced.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Clefts of the lip and palate are one of the most common congenital birth anomalies. Genetic factors play a great role in the etiology of them and the high percentage of the consanguineous marriage of the parents of the affected persons is one of the reasons. These defects not only make abnormal changes on appearance of the neonate, but also make a lot of stress and psychological problems for the patients and their families. Study on the prevalence of clefts, their risk factors and also genetic counseling for affected persons and their families can be a guideline for general population and probably reduce these anomalies over the generations.
Methods: Patients referred to the Department of Genetics, Imam Khomeini Hospital, Tehran, Iran were studied. A total of 7374 pedigrees of all the patients admitted to the Department, were studied during 2002-2005 and 99 pedigrees with the patients with cleft lip± palate or isolated cleft palate were separated. The total number of cases among these 99 pedigrees was 136. The effects of consanguineous marriage, positive family history and sex were investigated among cases.
Results: 70.8% of patients with syndromic clefts and 58.7% of patients with nonsyndromic CL±P had parents with consanguineous marriage. In addition 44.4% of patients with nonsyndromic CL±P had positive family history.
Conclusion: In our population prevalence of nonsyndromic CL±P was estimated to be 7 in 1000 (with 95% Confidence Interval was between 5 & 9) and prevalence of nonsyndromic CP was about 3.1 in 1000 (with 95% Confidence Interval was between 1.8 & 4.4). Consanguineous marriage of parents seems to have a significant role (p=0.02) on prevalence of the clefts.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Since the recognition of true number of human chromosomes in 1956, many techniques have been developed to detect chromosomal aberrations. A number of those, such as karyotyping and fluorescence in situ hybridization (FISH), are valuable tools in both research and diagnostics. But these techniques have defects that limit their application. One of the important limitations is resolution resolution limitations make it impossible to detect small aberrations. The other major defect is the disability to analyze whole genome. In 1997 Solinas-Toldo introduced a new technique that could cover other techniques' defects. This new technique called microarray-based comparative genomic hybridization (array CGH). Array CGH, with the powerful resolution of FISH and also the ability of whole genome analysis in single experiment accelerated the genetic research. Array CGH has resulted in to a great progress in oncology and genetic disorders research. In addition, this technique has the ability to be used in diagnostics too. This review article, witch include the data of recent published papers and our experiences, gives an overview of the array CGH and compare it with the other molecular cytogenetic techniques. Its application in oncology and genetic disorder is also discussed.

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Background: With approximately 386,000 deaths per year, esophageal cancer is the 6th most common cause of death due to cancer in the world. This cancer, like any other cancer, is the outcome of genetic alterations or environmental factors such as tobacco smoke and gastro-esophageal reflux. Tobacco smoking is a major etiologic factor for esophageal squamous cell carcinoma in western countries, and it increases the risk by approximately 3 to 5 folds. Chronic gastro-esophageal reflux usually leads to the replacement of squamous mucosa by intestinal-type Barrett’s metaplastic mucosa which is considered the most important factor causing esophageal adenocarcinoma. In contrast to esophageal adenocarcinoma, different risk factors and mechanisms, such as mutations in oncogenes and tumor suppressor genes, play an important role in causing esophageal squamous cell carcinoma. Molecular studies on esophageal cancers have revealed frequent genetic abnormalities in esophageal squamous cell carcinoma and adenocarcinoma, including altered expression of p53, p16, cyclin D1, EGFR, E-cadherin, COX-2, iNOS, RARs, Rb, hTERT, p21, APC, c-MYC, VEGF, TGT-α and NF-κB. Many studies have focused on the role of different polymorphisms such as aldehyde dehydrogenase 2 and alcohol dehydrogenase 2 in causing esophageal cancer. Different agents including bestatin, curcumin, black raspberries, 5-lipoxygenase (LOX) and COX-2 inhibitors have been found to play a role in inhibiting esophageal carcinogenesis. Different gene therapy approaches including p53 and p21WAF1 replacement gene therapies and therapy by suicide genes have also been experimented. Moreover, efforts have been made to use nanotechnology and aptamer technology in this regard.

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Background: Acute gastroenteritis is a major cause of morbidity and mortality among children in developing countries. Rotaviruses are recognized as the most common etiologic factors of gastroenteritis. In this study, we determined the epidemiologic features, clinical symptoms and molecular structure of rotavirus VP4(P) genotypes in children with acute diarrhea in Bahrami Hospital in Tehran Iran, during 2009 for justifying the routine use of rotavirus vaccines in children.

Methods: One hundred fifty fecal samples from 150 children with acute diarrhea in Bahrami Pediatric Hospital in Tehran, Iran were collected from January to December 2009. The patients’ mean age was 20.90+18.19 years (ranging from 1 month to 14 years). Fecal samples were transported on ice to the laboratory of virology department of Pasture Institute of Iran. The demographic and clinical data for each case were entered in an author-devised questionnaire. Group A rotavirus was detected by dsRNA-PAGE. Subsequently, rotavirus genotyping (VP4) was performed by semi-nested multiple RT-PCR and the phylogenetic tree of the Rotavirus nucleotides was constructed. The data were analyzed by statistical tests including Wilcoxon signed and Mann-Whitney U.

Results: Rotavirus was isolated in 19.3% of the samples, more than 90% of which had long RNA patterns. The predominant genotype (VP4) was P[8] (86%) and other genotypes respectively were P[6] (6.9%) and P[4] (6.9%).

Conclusion: A high prevalence of the P[8] genotype was found to be the cause of acute diarrhea. The analysis of P[8] genotype sequence showed a high level of similarity of the virus in this study with those of other Asian countries.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Gastric cancer is one of the most common diseases of digestive system with a low 5-year survival rate and metastasis is the main cause of death. Multi-factors, such as changes in molecular pathways and deregulation of cells are involved in the disease development. Epidermal growth factor receptor pathway (EGFR) which is associated with cell proliferation and survival can influence cancer development. EGFR function is governed by its genetic polymorphism thus, we aimed to study the tyrosine kinase domain gene mutations of the receptor in patients with gastric cancer.
Methods : In this experimental study, 123 subjects (83 patients with gastric cancer and 40 normal subjects) were investigated in north of Iran for EGFR gene polymorphisms during 1 year. Genomic DNA was extracted by DNA extraction kit according to the manufacture's protocol. Polymerase chain reaction single-stranded conformation polymorphism (PCR-SSCP) and silver staining were performed for investigating EGFR gene polymorphisms.
Results : The participants included 72 men and 44 women. Gene polymorphism in exon 18 was present in 10% of the study population but SSCP pattern in exon 19 did not show different migrate bands neither in patients nor in normal subjects.
Conclusion: It seems that screening for tyrosine kinas gene polymorphism of epidermal growth factor receptor in patients with gastric cancer and use of tyrosine kinas inhibitors could be useful in the prevention of disease progress and improvement of treatment process for a better quality of life in these patients.

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Background: True umbilical cord knot is one of the abnormalities of the umbilical cord. Active fetal movements create cord knotting. True umbilical cord knots are rare but may be associated with fetal distress and stillbirth. True umbilical cord knots are capable of impeding blood flow to the fetus.
Case presentation: A 26-year old primigravid woman was first treated for genital herpes simplex virus (HSV type 2) at 36 weeks of gestational age. She received oral acyclovir (400 mg three times daily for 10 days). At the gestational age of 38 weeks and 5 days, fetal activity decreased and NST was nonreactive. She was delivered by cesarean section and a true umbilical cord knot was found. Four years later, in her second pregnancy, another true knot was seen.
Conclusion: Excessively long umbilical cords are more likely to be associated with true knots. Genetics has an important role in determining cord length and occurrence of true knots.

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Cancer is one of the main reasons of mortality worldwide, and more than 90 percent of cancer deaths are due to metastasis. Although primary tumors are curable using chemical adjuvant therapy or surgery, metastatic tumors are mostly incurable. This resistance shows the high rate of mortality among patients with metastatic disease. Being a sequential event, metastasis is a subtle and intricate process in which tumor cells undergo a plenty of changes and acquire the capacity of migration, invasion, survival and self-renewal which all are necessary for metastasis to happen. The key point in recognition and cure in invasive cancers is to identify critical genes, proteins and pathways involved, and show their relation with each other and the disease. Forming metastasis needs favorable genetic and microenvironmental elements of tumor cells and distant tissue, respectively. Unfavorable conditions in each steps of this process lead to arresting metastasis and subsequent dormancy, which is the most important phenomenon in relapse. In this review, benefiting from tens of reliable and recently identified data and personal experiences, it has been tried to draw new patterns associated with metastasis for further investigation. Determining genes, proteins and microenvironmental factors that affect metastasis, in a sequential manner, can help better understanding of this lethal process and subsequently a prosperous treatment.

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Background: Gastric cancer is the most prevalent cancer with poor survival in gastrointestinal tract. Caspase 3 and 9 play an important role in the development and progression of cancer. Polymorphisms in the genes for these enzymes can affect gene activity and thus may influence susceptibility to gastric cancer. In this study, caspase 3 and 9 genes polymorphisms in patients with gastric cancer were examined.
Methods: In a case - control study, 100 patients with gastric cancer and 100 healthy individuals were evaluated in the region rs4647601: G> T for caspase-3 and -1263 A> G gene promoter for caspase 9. DNA extraction was performed from whole blood according to manufacture protocol. RFLP-PCR method was carrying out for detection of caspase 3 and 9 genes genotype in two groups.
Results: In this study, 143 men and 57 women were evaluated. All of them were selected from the same race and geographical area. The results indicated an increase of the mutant G allele in the control group, which leads to a decreasing in the incidence of gastric cancer (P<0.0001, OR: 0.096, (%0.95CL) =0.04-0.23).
Conclusion: It seems that screening of -1263 A> caspase 9 polymorphism could be a useful marker in personal sensitivity to gastric cancer and help to cancer treatment and prevention process. It is concluded that caspase gene variation may be a diagnostic factor in the gastric cancer.

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Background: Androgenetic alopecia (AGA) is the most common type of progressive balding that appears with early loss of hair, chiefly from the vertex. There has been significant relationship between AGA with coronary artery disease and related risk factors, such as hypertension in some studies. The aim of this study is to investigate the association between androgenetic alopecia with hyperlipidemia.
Methods: This cross-sectional study was performed on 112 patients with vertex type AGA (in male grade 3 or higher Hamilton- Norwood scale, and in female grade 2 or higher Ludwig scale) (study group) and 115 persons age and sex matched, with normal hair status (Normal group). None of participants had diabetes mellitus, hypothyroidism, liver disease, kidney disease and none of them had history of smoking and using drugs with effect on serum lipids. They were 20-35 years old and their body mass index were 20-30. Blood samples were obtained following 12 hours fasting status and serum levels of triglyceride (TG), cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) were determined using standard laboratory methods. Total cholesterol greater than 240 or TG greater than 200 or LDL greater than 160 or HDL less than 40 in men or HDL less than 50 in women were considered hyperlipidemia.
Results: In androgenetic alopecia group 46.4% and 47% of normal group were female. Mean (±SE) of total cholesterol (172.4±3.1, 148.8±3.1, P< 0.001), TG (133.6±5.5, 88.3±4.3, P< 0.001), LDL (96.4±2.9, 84.9±2.7, P= 0.004) and HDL (54.9±2.0, 45.5±0.9, P< 0.001) in AGA patients were higher than normal group. %46.4 of patients and %52.2 of controls had hyperlipidemia. Relationship between AGA with hyperlipidemia was not significant (P> 0.05).
Conclusion: The findings showed that there is no relationship between AGA and hyperlipidemia. Regarding to high levels of total cholesterol, LDL and triglyceride in AGA patients, it seems that, AGA increases risk of coronary heart disease. To determine a definite association between AGA and hyperlipidemia more studies are recommended.

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Background: A balanced reciprocal translocation is a structural abnormality, which at least consist of breakage of two non-homologous chromosomes along with pieces exchange and form quadrivalant structure that can produce unbalanced chromosomes during meiosis I and result in a fetus abortion. The aim of the present study is to offer using preimplantation genetic diagnosis (PGD) 24sure array, which delivers aneuploidy screening of 24 chromosomes, within a few hours to increase fertility and bearing a child without chromosomal abnormality of this couple. This technique could replace embryo donation for child bearing of this couple. Case presentation: A young couple with recurrent pregnancy loss in 6th and 7th week of pregnancy without family history of recurrent miscarriage and any clinical signs had conferred. All laboratory tests including hormonal, infections, semen and hysterosalpingography were normal except karyotype that showed balanced reciprocal translocation between chromosomes 5 and 18 in male. Chromosomal study of male parents showed normal karyotype. Conclusion: A balanced reciprocal translocation carrier is phenotypically normal, but during meiosis І, carrier chromosomes cant pair normally and form quadrivalant instead of bivalant that depend on type of their segregation (alternate, adjacent 1, adjacent 2,3:1,4:0), produce gametes that are chromosomally unbalanced which can result in early fetus abortion. Considering the number of abnormal gametes, the most effective way to help couples with this problem seems to be PGD 24sure, since it can identify reciprocal and Robertsonian translocation and allows concurrent screening of all chromosomes for aneuploidy. Another technique that can be compared with PGD 24sure is fluorescence in situ hybridization (FISH), but it has several technical limitations such as it is expensive and complexity, in addition it has only few probes (for chromosomes 21, 13, 18, X, Y) so sometimes necessary to create patient specific protocols.

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Background: Red Blood Cell's (RBC)’s folate may be related to decreased risk of colorectal adenoma. Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory enzyme in folate metabolism. The MTHFR C677T polymorphism is located in the Exon 4 region and is associated with the change of folate level. This study evaluated the associations between RBC’s Folate levels and colorectal adenoma risk, taking into account whether this associations is modified by MTHFR Polymorphism. Methods: In a case-control study conducted from January to October 2007 in Endoscopy-Colonoscopy ward of Shahid Faghihi Hospital, Shiraz. Participants were 177 case of colorectal adenoma who had pathologic-confirmed adenomatous polyps in full colonoscopy examination and 366 controls without polyps in full colonoscopy. Fasting venous blood were drawn from patients in order to determine RBC’s folate and to identify the MTHFR polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: Gender Distribution in the patient group were 57.6% male and 42.3% female and control group consisted of 55.1% male and 43.9% female. 50.2% of cases and 49.2% of controls were in the age group “45 years and above”. The T allele frequency was 56.6% in control group and 34.4% in colorectal adenoma patients. There was a significant association between T allele in -677 position of MTHFR gene and colorectal adenoma susceptibility (OR: 1.85, 95% CI: 0.76-4.24, P<0.001). Mean concentration of RBC’s folate was not statistically significant among three groups with TT genotype (mutation homozygote), CT genotype (heterozygote), and CC genotype (wild-type homozygote) (P>0.05) but mean concentration of RBC’s folate was the lowest in TT genotype compare with two other genotype. Odd's Ratio for low (<140ng/ml) versus high level of RBC’s folate in participants with TT genotype was (OR: 2.08, 95% CI: 0.10-2.19, P<0.05) as compare with the CC ones. Conclusion: The result of this study suggested an inverse association between RBC's folate concentration and colorectal adenomas risk, which may be more relevant for those with the MTHFR TT genotype.

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Background: Staphylococcus aureus is the most important cause of nosocomial infections acquired in the community. Protein A is a major component of Staphylococcus aureus cell wall. In analysis of the nucleotide sequence Protein A encoding spa, locus x consists of 24 base pairs which repeat with high polymorphism. In this study, the spa gene of Staphylococcus aureus isolated from clinical specimens were obtained from patients admitted to the hospital and healthy carriers. Methods: In a cross-sectional study, a total of 200 samples were collected. One hundred fifty samples were obtained from hospitalized patients and 50 samples obtained from staff nasal swabs in Hamadan University Hospitals from October 2013 to August 2014. Disk diffusion antibiotic susceptibility tests performed. The antibiotics studied were Vancomycin (30 µg), Cefoxitin (15 µg) Gentamicin (10 µg), Tetracycline (30 µg), Trimethoprim/sulfamethoxazole (25 µg), Ciprofloxacin (5 µg), Erythromycin (15 µg), Clindamycin (2 µg), Rifampin (5 µg). The tests performed according to the guidelines of clinical and laboratory standards institute (CLSI). It also detect the mecA gene of Methicillin-resistant Staphylococcus aureus strains (MRSA) and genes spa which encodes the protein A by polymerase chain reaction (PCR). The PCR products using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method with enzyme Rsa I (Afa I) were prepared. Results: This methicillin-resistant Staphylococcus aureus strain (MRSA) had the highest sensitivity and resistance to ciprofloxacin and clindamycin. Totally, 8 amplicon with different sizes for the spa gene were identified. A total of 9 patterns polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) were found. Some of these patterns between Staphylococcus aureus isolated from clinical specimens and nasal carriers were common. Conclusion: There is a similar pattern of spa gene among patients admitted to the hospital and staff, according to our findings. Analysis of the patterns can reduced transmission of infection in both hospital staff and patients. Also it can help the physicians for correct management of infections.

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Background: Cytotoxic lymphocyte antigen-4 (CTLA-4) plays an important role in regulating T cell activation. CTLA-4 gene polymorphisms are related with genetic susceptibility to various autoimmune diseases, including systemic lupus erythematosus (SLE). We analyzed the role of CTLA-4 polymorphisms at positions -318CT in patients who suffer from SLE. Methods: This study was performed on 180 SLE patients referred to 5th Azar University Hospital in Gorgan, Iran. Three hundred and four ethnically-and age-matched healthy controls with no history of autoimmune diseases entered the study between 5th May 2008 and 23rd October 2009. DNA was extracted from blood samples according to the standard procedure. Polymerase chain reaction- restriction fragments length polymorphism (PCR-RFLP) was used to analyze the genotype and allele frequencies of this polymorphism. PCR was carried out using the following primers: forward 5′-AAATGAATTGGACTGGATGGT-3′ and reverse 5′-TTACGAGAAAGGAAGCCGT G-3′. The frequency of alleles and genotypes were assessed using direct counting. Chi-square test and Fisher’s exact test were used to compare the association between the alleles and genotype frequencies and SLE. P<0.05 were considered statistically significant. Results: The CC genotype was observed in 94.5% of the SLE patients and 82.4% of the controls the difference was statistically significant (P=0.0001, OR=3.51, CI95%=1.77-7.53). The CT genotype, on the other hand, was more frequently observed in the control group (17.1% vs. 5.5%, P=0.0001, OR=0.28). T allele was significantly more common in the controls compared to SLE patients (P=0.0001, OR=0.26, CI95%=0.13-0.53). Conclusion: Our results suggest that the -318C/T polymorphism of CTLA-4 gene might play a significant role in the genetic susceptibility to SLE. Therefore, further studies on populations, especially from other Middle East countries, are needed to confirm our results.

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Stem cells are undifferentiated and multi pluripotent cells which can differentiate into a variety of mature cells and tissues such as nervous tissue, muscle tissue, epithelial tissue, skeletal tissue and etc. Stem cells from all different source have three unique features: 1) Proliferative capability: Stem cells are capable of self dividing and self renewing for long periods or more than six months at least that called immortalization. 2) Undifferentiated nature: It’s considered as one of the essential characteristics of stem cell, so it doesn't have any tissue-specific construction. 3) Differentiation to the different cells from all organs: This ability can Induced by tissue specific transcription factors. Because of that, they are so important in prevention and treatment of human disease. Depending on the sources from which they derive, they have different types which can be used to produce special cells and tissues. The most significant types of stem cells are; embryonic stem cells (ESCs) which are derived from embryos, adult stem cells (ASCs) which are derived from differentiated cells in a specific tissue, induced pluripotent stem cells (iPSs) which are produced from adult differentiated cells that have been genetically reprogrammed to act resemble to an embryonic stem cell and cord blood stem cells which contains haematopoietic stem cells and derived from the umbilical cord after gestation. By providing a medium containing of special growth factor, it is possible to orientated stem cell differentiation pathway and gained certain cells from them. The important uses of stem cells includes damaged heart tissue cells improvements and bone tissue repairing, cancer treatment, damaged neurological and spinal tissue repairing, improving burns and injuries and the treatment of diabetes, infertility and spermatogenesis dysfunction. Furthermore, the application of them in gene therapy is an important issue in the modern medicine science due to the role of them in transferring gene into different cells. Today, this method have had considerable progress in the treatment of many disease. In this review study, some aspect of stem cells like types and characteristic, origin, derivation techniques, storage conditions and differentiation to target tissues, current clinical usage and their therapeutic capabilities will be discussed.

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Background: Obesity is one of the most important problems in developed countries and cause cardiovascular diseases, diabetes and hypertension. The complex phenotype influenced by both genetic and the environment factors. One of the most important genes which is effective in this phenotype is peroxisome proliferator-activated receptor gamma (PPAR-γ). This study was carried out of investigate the association of Pro12Ala (rs1801282) polymorphism in mentioned gene with obesity in Tehran Lipid and Glucose Study (TLGS).

Methods: The present study done in September 2014 in Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences. For the present case-control study 239 subjects with excess weight and body mass index more than 30 kg/m2 as a case and 240 subjects with normal weight and body mass index less than 25 kg/m2 as a control were selected. The rs1801282 was proliferated, detected and genotyped using tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method.

Results: The results indicated that there was significant association between the presence of risk allele G of rs1801282 and obesity disease in the TLGS population (P=0.000). Genotype and allelic frequencies of rs1801282 in patient and healthy group were: 55.2% and 23.8% for GG, 24.3% and 30.4% for GC, 20.5% and 45.8% for CC, 67% and 39% for G, 33% and 61% for C, respectively.

Conclusion: The results of study indicated that the presence of G allele could be increase 1.7 the risk of obesity. These differences in patient and healthy group lead us to select this marker as a genetic marker to predict the risk of obesity. There are statistical differences between the distribution of mentioned polymorphism in Tehranian population and other populations. However, replicating the study in a larger population of Tehranian people with more affected cases is suggested to generalize the results of this study.

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Stable molecular changes during cell division without any change in the sequence of DNA molecules is known as epigenetic. Molecular mechanisms involved in this process, including histone modifications, methylation of DNA, protein complex and RNA antisense. Cancer genome changes happen through a combination of DNA hypermethylation, long-term epigenetic silencing with heterozygosis loss and genomic regions loss. Different combinations of N-terminal’s changes cooperate with histone variants with a specific role in gene regulation. It have led to load a setting histone that determine transcription potential of a particular gene or genomic regions. DNA methylation analysis in genome region using methylation-specific digital karyotyping of normal breast tissue detect gene expression patterns and DNA specific methylation can be found in breast carcinoma too more than 100 genes in breast tumors or cell lines of breast cancer are reported hypermethylated. Important of DNA methylation on cancer has been concentrated CpG islands hypermethylation. Most of the techniques are able to identify hypermethylated areas. Often, methylated genes play important role in cell cycle regulation, apoptosis, metastasis and tissue invasion, angiogenesis and hormonal signaling. Cyclin D2 (CCND2) gene is an important regulator of cell cycle and increased of expression inhibits the transition from G1 to S cell cycle. This gene is frequently methylated in breast cancer and has been proposed as the first event. Other cell cycle regulator is p16ink4A / CDKN2A that methylated in a large number of human cancers, including breast cancer. Another regulator of the proliferation of breast cancer that methylated is tumor suppressor RAR-β cancer that has been found in lobular and ductal carcinoma. Recent studies have showed the role of epigenetic silencing in the pathogenesis of breast cancer in which tumor suppressor genes have been changed by acetylation and DNA deacetylation. Histone deacetylase inhibitors have different roles in cancer cells and could show the ways of new treatment for breast cancer. In this review, various aspects of breast cancer epigenetics and its applications in diagnosis, prediction and treatment are described.