Tehran University Medical Journal

---

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.

---

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.

---

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.

---

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.

---

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.

---