Different Effects of Low-Level Laser Therapy on the Proliferation of HT29 Cells in Culture and Xenograft Models.

Introduction: Different kinds of treatments have been developed to fight cancers. Low-level laser therapy (LLLT), also known as photobiomodulation therapy (PBMT), is a low-power monochromatic and coherent light that has been used successfully for healing injuries and combating malignancies. However, there are concerns about the application of LLLT to cancers due to the increased proliferation of some cancer cells after LLLT. Methods: This study investigated the effects of 650 nm and 870 nm lasers on the proliferation of HT29 colorectal cancer cell lines in vitro and in vivo. Results: The results showed that the laser with a wavelength of 870 nm did not meaningfully alter the proliferation of cultured cells. However, cell proliferation was promoted when the laser was applied within a wavelength of 650 nm. Treatment of HT29-derived tumors in nude mice with the 650 nm laser resulted in the decline of the tumor progression rate compared to controls. This result was inconsistent with the proliferative effects of the laser on the cultured cells. Conclusion: Cell behavior in response to LLLT might be different between cell culture and xenograft models.

Identification of a TPP1 Q278X Mutation in an Iranian Patient with Neuronal Ceroid Lipofuscinosis 2: Literature Review and Mutations Update.

Neuronal ceroid lipofuscinoses type 2 (CLN2), the most common form of Batten disease, is caused by TPP1 loss of function, resulting in tripeptidyl peptidase-1 enzyme deficiency and cerebral accumulation of lipopigments. Clinical hallmarks include epileptic seizures, vision loss, progressive movement disorder, ataxia, and eventually death. Diagnosis is often delayed due to the rarity of the conditions. Results: Here, we report a case presenting with clinical features of CLN2, carrying a homozygous novel nonsense variant in TPP1 (NM_000391:c.C832T, (p.Q278*), rs1352347549). Moreover, we performed a comprehensive literature review regarding previously identified disease-causing TPP1 mutations and genotype-phenotype correlations. Conclusion: Depending on the type of mutation, different phenotypes are observed in patients with CLN2, suggesting that the severity of phenotypes is related to the genotype of the patients.

Association of Genetic Polymorphisms in GSTP1, GSTM1, and GSTT1 Genes with Vesicoureteral Reflux Susceptibility in the Children of Southeast Iran.

BACKGROUND: Vesicoureteral reflux (VUR) disease is the most common type of urinary tract anomalies in children. Genetic risk factors may be associated with the etiology of VUR. The role of the Glutathione S-transferases (GSTs) as multifunctional enzymes is cellular oxidative stress handling. This is the first study aimed at evaluating the relative risk of GSTP1, GSTM1, and GSTT1 polymorphisms in VUR susceptibility in children and provides new important insights into the genetics of affected children. METHODS: The study was done in 2013 in Sistan and Baluchestan University, eastern Iran. Genotyping of three GSTP1, GSTM1, and GSTT1 genes were determined using the multiplex polymerase chain reaction assay in 216 reactions for 72 VUR children and 312 reactions for 104 healthy controls. RESULTS: The presence of GSTT1 deletion was associated with high risk of VUR in children, whereas GSTP1 and GSTM1 genotypes did not show the same effect. Furthermore, the combination of GSTT1/GSTM1 and GSTT1/ GSTP1 genotypes showed a significant influence on lower risk of VUR in children. CONCLUSION: Deletion of GSTT1 functional gene is a genetic risk factor causing VUR in children. Interestingly, the combination of GSTM1 and GSTP1 null genotypes with GSTT1 has shown a protective role against risk of GSTT1 deletion.

Expression of Long Non-Coding RNAs in Placentas of Intrauterine Growth Restriction (IUGR) Pregnancies.

BACKGROUND: Intrauterine growth restriction (IUGR), a pathologic diminution of the rate of fetal growth, has been associated with alterations in expression of several genes. However, the role of long non-coding RNAs (lncRNAs) in its pathogenesis has not been studied. METHODS: In this study we evaluated the expression of four lncRNAs namely, nuclear paraspeckle assembly transcript (NEAT1), taurine up-regulated 1 (TUG1), p21-associated ncRNA DNA damage-activated (PANDA), and metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) in placenta samples obtained from IUGR and normal pregnancies to determine their possible contributions in the pathogenesis of IUGR. RESULTS: We found no significant differences in expression levels between cases and controls. We also found no correlation between expression and clinical data of study participants; however, we found significant correlations between expression levels of all the assessed lncRNAs in both cases and controls. CONCLUSION: These results imply the existence of a possible shared regulatory mechanism for the expression of these transcripts in placenta. Future studies are needed to perform such evaluations in larger sample sizes or in animal models in earlier stages of pregnancy.

Identification of a homozygous GFPT2 variant in a family with asthenozoospermia.

PURPOSE: Asthenozoospermia (ASZ) is a condition characterized by reduced sperm motility in semen affecting approximately 19% of infertile men. Major risk factors, particularly gene mutations, still remain unknown. The main aim of the present study was to identify novel genes and mutations that may influence human sperm motility. METHODS: Whole-exome sequencing (WES) was performed on a large pedigree of infertile men (n = 5) followed by bioinformatics analyses. Candidate pathogenic variants were screened in a control cohort of 400 ancestry-matched Iranian fertile men, 30 unrelated men with idiopathic ASZ, and public databases. RESULTS: A rare mutation in GFPT2 gene (c.1097G > A; p.Arg366Gln) located in the SIS 1 domain was segregated with the phenotype and was consistent with autosomal recessive inheritance. The in silico analyses revealed that the mutation might affect the function of SIS 1 domain and abolish its carbohydrate-binding ability. CONCLUSION: Homozygosity of the GFPT2 p.Arg366Gln mutation was associated with increased levels of reactive oxygen species (ROS) in spermatozoa and decreased sperm motility.

Involvement of the Dysregulation of miR-23b-3p, miR-195-5p, miR-656-5p, and miR-340-5p in Trastuzumab Resistance of HER2-Positive Breast Cancer Cells and System Biology Approach to Predict Their Targets Involved in Resistance.

Resistance to trastuzumab has become a limiting factor for therapeutic efficacy of human epidermal growth factor 2 (HER2)-positive breast cancer. Different expression levels of miRNAs in cancer cells have been associated with poor prognosis and response to chemotherapy. The aim of this study was to evaluate miRNAs that were thought to be associated with HER2-positive breast cancer chemoresistance. In this study, the relative expression of candidate miRNAs to U6 RNA was evaluated in trastuzumab-resistant and trastuzumab-sensitive cells using relative real-time PCR. Our results demonstrated that miR-23b-3p, miR-195-5p, miR-656-5p, and miR-340-5p were significantly dysregulated. For the first time in this study, these miRNAs were identified to be involved in trastuzumab resistance. TargetScan and miRDB were then used for predicting the potential targets of the candidate miRNAs. Our results also revealed that the predicted potential targets of these miRNAs were strongly associated with drug resistance pathways. As a relative expression of candidate miRNAs was statistically different in trastuzumab-resistant and trastuzumab-sensitive cells, their potential targets were involved in drug resistance pathways. We strongly hypothesized the dysregulation of miRNAs as a possible mechanism of trastuzumab resistance. We also assumed that the strategic manipulation of these regulatory networks might be a possible therapeutic strategy to improve the results of chemotherapy for this resistance. However, more research is needed to evaluate the role of these miRNAs in the acquisition of trastuzumab resistance.

Mimicry and well known genetic friends: molecular diagnosis in an Iranian cohort of suspected Bartter syndrome and proposition of an algorithm for clinical differential diagnosis.

BACKGROUND: Bartter Syndrome is a rare, genetically heterogeneous, mainly autosomal recessively inherited condition characterized by hypochloremic hypokalemic metabolic alkalosis. Mutations in several genes encoding for ion channels localizing to the renal tubules including SLC12A1, KCNJ1, BSND, CLCNKA, CLCNKB, MAGED2 and CASR have been identified as underlying molecular cause. No genetically defined cases have been described in the Iranian population to date. Like for other rare genetic disorders, implementation of Next Generation Sequencing (NGS) technologies has greatly facilitated genetic diagnostics and counseling over the last years. In this study, we describe the clinical, biochemical and genetic characteristics of patients from 15 Iranian families with a clinical diagnosis of Bartter Syndrome. RESULTS: Age range of patients included in this study was 3 months to 6 years and all patients showed hypokalemic metabolic alkalosis. 3 patients additionally displayed hypercalciuria, with evidence of nephrocalcinosis in one case. Screening by Whole Exome Sequencing (WES) and long range PCR revealed that 12/17 patients (70%) had a deletion of the entire CLCNKB gene that was previously identified as the most common cause of Bartter Syndrome in other populations. 4/17 individuals (approximately 25% of cases) were found to suffer in fact from pseudo-Bartter syndrome resulting from congenital chloride diarrhea due to a novel homozygous mutation in the SLC26A3 gene, Pendred syndrome due to a known homozygous mutation in SLC26A4, Cystic Fibrosis (CF) due to a novel mutation in CFTR and apparent mineralocorticoid excess syndrome due to a novel homozygous loss of function mutation in HSD11B2 gene. 1 case (5%) remained unsolved. CONCLUSIONS: Our findings demonstrate deletion of CLCNKB is the most common cause of Bartter syndrome in Iranian patients and we show that age of onset of clinical symptoms as well as clinical features amongst those patients are variable. Further, using WES we were able to prove that nearly 1/4 patients in fact suffered from Pseudo-Bartter Syndrome, reversing the initial clinical diagnosis with important impact on the subsequent treatment and clinical follow up pathway. Finally, we propose an algorithm for clinical differential diagnosis of Bartter Syndrome.

MAML1 regulates EMT markers expression through NOTCH-independent pathway in breast cancer cell line MCF7.

Tumor relapse is the main cause of breast cancer related deaths and metastasis due to epithelial-mesenchymal transition (EMT) having a critical role in this process. MAML1 is the main co activator of NOTCH signaling pathway and its role in EMT remains unknown. In this study, this role was evaluated through overexpression and knockdown study of MAML1 in MCF7 and MDA-MB-231 cells. MAML1 overexpression up regulated the epithelial and down regulated the mesenchymal markers. In addition, MAML1 silencing decreased epithelial and increased mesenchymal markers. Notch inhibition using γ-secretase inhibitor resulted in increased E-cadherin expression. MAML1 ectopic expression, further increased E-cadherin expression with inhibition of NOTCH signaling. Wound healing assay showed that MAML1 overexpression decreases the rate of migration, while MAML1 silencing increases this rate significantly. In conclusion, our data indicated that MAML1 negatively regulates EMT markers expression in breast cancer cells.

Analysis of Polymorphism and Expression Profile of ASIC1 and IL-6 Genes in Patients with Gastric Cancer

Gastric cancer is one of the most common upper gastrointestinal malignancies. Some Iranian provinces, such as in the northern and northwestern areas, are at a high risk, whereas the central and western provinces are at a medium and the southern regions at low risk. This study was carried out to estimate the impact of the expression patterns of ASIC1 and IL-6 genes and the IL-6rs-174 and ASIC1rs 75624685 polymorphisms in the pathogenesis of gastric cancer. Materials and methods: Tetra-ARMS PCR was employed to analyze the polymorphism status of the ASIC1 and IL-6 genes with 85 paraffin-embedded tissue blocks from cases and 117 normal blood samples as controls. We also investigated mRNA expression levels of these genes in 12 cases and controls using real-time PCR. Results: Our results showed a significant association between expression of ASIC1 and elevated risk of gastric cancer (p<0.001).

Comparison of two different media for maturation rate of neural progenitor cells to neuronal and glial cells emphasizing on expression of neurotrophins and their respective receptors.

Neural cells derived from embryonic stem cells (ESCs) have potential usefulness for the treatment of neurodegenerative disorders. Modulation of intrinsic growth factors expression such as neurotrophins and their respective receptors by these cells is necessary to obtain functional neural cells for transplantation. In present study, we compared neural differentiation potential of two different media, NB + 5%ES-FBS + N2B27 and Ko-DMEM + 5%ES-FBS for conversion of mESC derived neural progenitors (NPs) into mature neural cells with emphasis on effect of the these two media on neurotrophins and their respective receptors expression. Immunofluorescence staining, RT-qPCR and western blot analysis showed that the expression of neuronal specific markers, MAP2 and Tuj-1, in NB + 5%ES-FBS + N2B27 medium was significantly higher than the other medium. Western blot assay revealed that the expression of BDNF and NGF increased significantly in mature neural cells obtained from NB + 5%ES-FBS + N2B27 medium but decreased in neural cells from Ko-DMEM + 5%ES-FBS medium compared to mESCs. TrkB protein was not detectable in mESCs but its expression increased in neural cells obtained from both media although its expression in NB + 5%ES-FBS + N2B27 medium was significantly higher than the other medium. In contrast to TrkB, p75NTR protein was detectable in mESCs and is remained constant in neural cells cultured in NB + 5%ES-FBS + N2B27 medium but decreased significantly in the other medium. In conclusion, our results indicated that NB + 5%ES-FBS + N2B27 medium promoted neural differentiation process of mESCs and caused enhancement of neurotrophins protein expression in addition to their cognate receptors.

Association of CTLA-4 gene polymorphisms -318C/T and +49A/G and Hashimoto's thyroidits in Zahedan, Iran.

Hashimoto's thyroiditis (HT) is a chronic inflammation of the thyroid gland and is known as the most common autoimmune disease. Development of autoimmune destruction of thyroid cells is a multi-step process involving convergence of genetic and environmental factors. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) has an important role in homeostasis and negative regulation of immune responses, and is therefore considered to be a key element in the development of autoimmune diseases. The present study evaluated the association of the CTLA-4 gene polymorphisms 318C/T (rs5742909) and +49A/G (rs231775) with HT in an Iranian population (including 82 patients with HT and 104 healthy controls who were referred for routine premarital blood screenings). Genotyping was performed using the tetra-primer amplification refractory mutation system polymerase chain reaction technique. No significant differences were observed in genotype and allele frequencies in the single nucleotide polymorphisms (SNPs) between cases and controls. In the cases as well as in the controls, the TT genotype in the -318C/T polymorphism was absent and the predominant genotype was CC, while the predominant genotype for the +49A/G SNP was AA. As only few studies in this field have assessed Iranian and even Middle Eastern populations, additional studies with a higher number of samples are recommended to further assess the impact of -318C/T (rs5742909) and +49A/G (rs231775) polymorphisms of CTLA-4 on HT.

Contribution of LATS1 and LATS2 promoter methylation in OSCC development.

The aberrant DNA methylation of the tumor suppressor genes involved in DNA Damage Response (DDR) signaling and cell cycle regulation may lead to the tumorigenesis. Our purpose here is to analyze the promoter methylation and mRNA expression levels of LATS1 and LATS2 (LATS1/2) genes in OSCC. Promoter methylation status of LATS1/2 genes was evaluated in 70 OSCC paraffin-embedded tissues and 70 normal oral samples, using Methylation Specific PCR (MSP). LATS1/2 mRNA expression profiles were also investigated in 14 OSCC patients and 14 normal samples, using real-time PCR. In both candidate genes, promoter methylation assessment revealed significant relationship between cases and controls (OR = 2.24, 95 % CI = 1.40-3.54, P = 0.001; LATS1 and OR = 15.5, 95%CI = 3.64-64.76, P < 0.001; LATS2). As well as, the evaluation of mRNA expression levels showed decreased expression in OSCC tissues in compare to control tissues. (Mean ± SD 1.74 ± 0.14 in OSCC versus 2.10 ± 0.24 in controls, P < 0.001; LATS1 and Mean ± SD 1.36 ± 0.077 in OSCC versus 1.96 ± 0.096 in controls, P < 0.001; LATS2). To the best our knowledge, this is the first report regarding the down-regulation of LATS1/2 through promoter methylation in OSCC. It is suggested to explore the down-stream transcription factors of both genes for finding the molecular mechanism of this deregulation in OSCC.

Analysis of IL-33 gene polymorphism (rs11792633 C/T) and risk of schizophrenia.

Recently, inflammation has been found to be a significant factor in the development of Schizophrenia (SCZ). The aim of the present research was to investigate whether interleukin-33 (IL-33, OMIM: 608678) gene polymorphism (rs11792633, C/T) is associated with the development of SCZ or not. DNA was isolated from the serum of 70 patients with SCZ and 70 healthy controls. The PCR based method was used for detection of the IL-33 polymorphism. The CT (OR=0.05, 95% CI: 0.003-0.057, P<0.001) and TT (OR=0.12, 95% CI: 0.028-0.46, P<0.001) genotypes significantly decreased the risk of SCZ. Our present findings indicate that the IL-33 polymorphism associated with the risk of SCZ.

Haplotype analysis of BRCA1 intragenic markers in Iranian patients with familial breast and ovarian cancer.

BACKGROUND: Breast cancer is the most common malignancy in women. Breast Cancer Type 1 Susceptibility gene (BRCA1) is a tumor suppressor gene, involved in DNA damage repair and in 81% of the breast-ovarian cancer families were due to BRCA1. In some clinically investigated genes, the intragenic marker polymorphism is important and the screening of such mutations is faster by using short tandem repeat (STR) polymorphism. Individual polymorphism of STR is a good evidence for following inheritance of repeat polymorphism. OBJECTIVE: The aim of this study was to evaluate three intragenic BRCA1 marker polymorphisms in families, which have two or more patients with breast/ovarian cancer in comparison to healthy women. MATERIALS AND METHODS: A total of 107 breast and/or ovarian cancer patients and 93 unrelated healthy women with no clinical phenotype of any malignancy or familial cancer history constitute the study groups. Haplotyping analysis, at 3 intragenic BRCA1 microsatellite markers (D17S855, D17S1322 and D17S1323), were performed for all subject and control groups using labeled primers. RESULTS: After fragment analysis, significance differences were observed as follows: two alleles of D17S855; allele 146 (p=0.02) and 150 (p=0.006), and two alleles of D17S1322, allele 121 (p=0.015) and 142 (p=0.043). These differences were compared with control group. There was significance difference in 8 di/tri allelic haplotypes in present experimental subjects. Some haplotypes were observed to have approximately twice the relation risk for breast cancer. CONCLUSION: According to recent results, assessment of presence or absence of mentioned alleles in BRCA1 microsatellite can be used for prognosis in individuals, suspected of having or not having the breast cancer.

Analysis of the IL-10, IL-12, and TNF-α Gene Polymorphisms in Patients With Vesicoureteral Reflux Among the Southeast Iranian Population.

BACKGROUND: Vesicoureteral reflux (VUR) is a common childhood disorder that is characterized by the abnormal movement of urine from the bladder into the ureters or kidneys. OBJECTIVES: The aim of this study was to determine whether the genetic polymorphisms of the IL-10, IL-12, and TNF-α genes are involved in the development of VUR. PATIENTS AND METHODS: The tetra amplification mutation refractory system-polymerase chain reaction (Tetra-ARMS PCR) was applied to analyze the four polymorphic sites of the IL-10AG-1082, IL-10CA597, IL-12CA1188, and TNF308GA genes in 124 VUR children and 110 healthy controls. RESULTS: A significant, highly increased risk of VUR disease was found for the CA, AA, and combined genotypes of IL-10CA597 (OR = 5.2, 95% CL: 1.80 - 18.25; P = 0.0006, OR = 9.1, 95% CL: 1.11 - 122.75; P = 0.02, OR = 5.3, 95% CL: 1.82 - 18.61; P = 0.00052, respectively); the AG, GG, and AG + GG genotypes of IL-10AG-1082 (OR = 12.8, 95% CL; 2.9 - 113.9; P = 0.00003, OR = 12.62, 95% CL: 2.93 - 114.53; P = 0.00003, respectively); and the AA genotype of IL-12 (AA, OR = 0.19, 95% CL: 0.5 - 0.55; P = 0.0006). The frequency of the C allele in both IL-10CA and IL-12CA was greater in patients with VUR than in the healthy controls. No association was found between TNF308GA and the risk of VUR. CONCLUSIONS: The results demonstrated significant associations between the IL-10 (AG-1089, IL-10CA) and IL-12 (AA) gene polymorphisms and a highly increased risk of VUR.

Evaluation of LATS1 and LATS2 Promoter Methylation with the Risk of Pterygium Formation.

Purpose. Pterygium is a serious eye problem in countries with high exposure to UV. However, despite numerous studies, the molecular etiology of pterygium is unclear. Recent studies have indicated that LATS1 and LATS2 genes are involved in DDR signaling pathways against continuous UV exposure. Our aim was to evaluate the LATS1 and LATS2 promoter methylation with the risk of pterygium formation. Methods. We evaluated the promoter methylation status of LATS1 and LATS2 using methylation-specific PCR technique. Also, mRNA expression of LATS1 and LATS2 was assessed in 14 cases of pterygium and 14 normal specimens by real-time PCR. Results. Promoter methylation of LATS1 and LATS2 was detected significantly between pterygium tissues and normal tissues [LATS1; OR = 4.9; 95% CI: 1.54 to 15.48, P = 0.003; LATS2; OR = 7.1; 95% CI: 1.53 to 33.19, P = 0.004]. The gene expression analysis showed a statistically significant difference between pterygium tissues and healthy controls for both LATS1 and LATS2 (P < 0.05). Conclusions. The data of this study is the first report regarding the effect of promoter methylation of the LATS1 and LATS2 in the pterygium. To confirm these data, doing further studies in various genetic populations with large sample sizes using advanced molecular techniques is proposed.

A novel approach to investigation of the pathogenesis of pterygium based on assessment of promoter hyper-methylation and expression profile of CTLA4 gene: A credible report of CTLA4 gene expression in human eye tissue.

BACKGROUND: Pterygium is the human eye lesion whose prevalence in the general population is estimated about 2%. The disease, in extreme phase, can lead to visual disturbance and eventually causes complete loss of vision due to the lesion growth over the papillary axis. Pterygium invasive tissue is a tumor-like tissue that is initially identified and then is attacked by cytotoxic T cells. Cytotoxic T lymphocyte associated antigen 4 (CTLA4), as a modulator molecule of the adaptive immune system, plays a critical role in maintaining peripheral T cell tolerance by diminishing its responsiveness and increasing its activation threshold. The aim of this study is to investigate the association between some epigenetic changes of the CTLA4 gene, such as promoter methylation and gene expression, and pathogenesis of pterygia. MATERIALS AND METHODS: Genomic DNA was extracted from 75 formalin-fixed, paraffin-embedded tissues of pterygia and 70 specimens of normal conjunctiva from eyes without pterygium as the control group, collected from Sistan and Baluchestan population. CTLA4 gene promoter methylation was carried out by methylation-specific PCR technique. The gene expression analysis was done on extracted total RNA from 20 healthy and 23 pterygium tissue samples using Real-Time PCR technique. RESULTS: Promoter methylation changes of CTLA4 gene were not statistically different in patients with pterygium in comparison with healthy controls (OR=1.614; 95% CI=0.57-4.75; P value=0.37). However, gene expression level of CTLA4 was remarkably different in patients and healthy controls (Mean±SD: 1.343±0.133 and 2.027±0.219, respectively; P value=0.009). CONCLUSION: This is a credible evidence of CTLA4 gene expression in human eye tissue. This first hand attempt of investigating the association of epigenetic changes of the CTLA4 gene and pathogenesis of pterygia, indicated a significant intensification of the gene expression of CTLA4 in patients with pterygia. We suggest that increasing CTLA4 gene expression can be a trigger which promotes pterygium enlargement. However, further studies on more populations with larger sample sizes need to be done to verify this hypothesis in the future.

Relationship between phosphoinositide-3-kinase genetic polymorphism and schizophrenia.

UNLABELLED: Schizophrenia, with incidence of 1% worldwide, is a common mental disorder. Phosphoinositide-3-kinases (PI3Ks) are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, intracellular trafficking, and survival. These enzymes play an important role in the PI3K/AKT signalling pathway. The PIK3CA gene encodes the alpha catalytic subunit of the PI3K enzyme. The present study analysed the role of three SNPs of the PIK3CA gene (rs6443624 (A/C), rs7640662(C/G) and rs7621329(C/T)) in the development of schizophrenia. METHODS: In this case-controlled study, DNA was extracted from blood samples from 108 patients with schizophrenia and 108 healthy patients as controls. Genotypic analyses of PIK3CA SNPs rs6443624 (A/C), rs7640662(C/G) and rs7621329(C/T) were made using the tetra primer ARMS-PCR technique. RESULTS: The outcome shows significant difference between CT and the combined genotype (CT + TT) of rs7621329 and the risk of schizophrenia (OR = 6.4, 95% CI = 3.023-14.23, p < 0.0001). Outcome showed no significant difference for were for analyses of the rs6443624 and rs7640662 genotypes. CONCLUSIONS: These results indicate an association between PIK3CA gene polymorphism on the rs7621329(C/T) site and the risk of schizophrenia. Further study of the genetic population using a larger sample size is necessary in order to validate these present findings.

Assessment of Promoter Hypermethylation and Expression Profile of P14ARF and MDM2 Genes in Patients With Pterygium.

BACKGROUND: Pterygium is a fairly general condition in many regions of the world. The cause of this abnormality is still ambiguous. However, recent findings suggest that pterygium is a benign progressive tissue and not a degenerative disorder. The main goal of our study was to investigate the effects of P14 and MDM2 promoter methylation on the risk of pterygium. MATERIALS AND METHODS: In this study, the DNA of 81 primary pterygium and 75 normal conjunctiva tissues was extracted and modified for the assessment of methylation of P14 and MDM2 promoters by methylation-specific polymerase chain reaction (MSP). We also estimated the mRNA expression levels of these genes in 23 pterygium and 18 normal conjunctiva tissue samples using real-time quantitative reverse transcriptase polymerase chain reaction. RESULTS: The frequency of methylation for P14 was 92.6% for cases and 97.3% for controls. MDM2 gene methylation at the promoter site was 39.5% and 72.0% for pterygium and normal conjunctiva tissues, respectively. So statistically, a significant relationship between MDM2 gene promoter methylation and the risk of disease was found (odds ratio=5.3; 95% confidence limit, 2.6-10.8; P<0.0001). In addition, the expression of MDM2 gene has increased in pterygium (1.371548±0.6727) in comparison with conjunctiva tissues as control (1.20621±1.0) (P<0.05), but it was not significant for P14 gene. CONCLUSION: Our results have indicated that hypomethyaltion and overexpression of MDM2 gene take place in patients with the pterygium. To confirm the presented data, suggesting further studies with a larger sample size in various genetic populations.

Promoter Methylation and BDNF and DAT1 Gene Expression Profiles in Patients with Drug Addiction.

BACKGROUND: Drug addiction is a brain disorder that has negative consequences for individuals and society. Addictions are chronic relapsing diseases of the brain that are caused by direct drug-induced effects and persevering neuroadaptations at the epigenetic, neuropeptide and neurotransmitter levels. Because the dopaminergic system has a significant role in drug abuse, the purpose of this study was to analyze the methylation and expression profile of brain-derived neurotrophic factor (BDNF) and dopamine transporter (DAT1) genes in individuals with drug addiction. MATERIALS AND METHODS: BDNF and DAT1 promoter methylation were investigated with a methylation-specific polymerase chain reaction (PCR) technique in blood samples from 75 individuals with drug addiction and 65 healthy controls. The expression levels of BDNF and DAT1 were assessed in 12 mRNA samples from the blood of patients and compared to the samples of healthy controls (n = 12) with real-time quantitative reverse transcription PCR. RESULTS: No significant differences were found in the methylation of BDNF and DAT1 between patients and controls, but the relative levels of expression of BDNF and DAT1 mRNA differed significantly in the patients compared to controls (p < 0.0001). CONCLUSION: These results showed that the methylation status of the BDNF and DAT1 genes had no significant function in the processes of drug addiction.