[show abstract][hide abstract] ABSTRACT: Objective
Functional polymorphisms within vascular endothelial growth factor (VEGF) gene have shown association with various conditions including diabetic neuropathy and retinopathy. In this study we have performed a candidate gene association study in order to examine VEGF gene polymorphism association with diabetic foot ulcer (DFU).
[show abstract][hide abstract] ABSTRACT: Several pieces of evidence support the involvement of immune system in Menière's disease (MD). Macrophage migration inhibitory factor (MIF) plays a key role in immune-mediated reactions. Several studies have shown an association between MIF gene polymorphisms and susceptibility to various inflammatory and autoimmune disorders. The aim of this study was to explore the association between MIF-173 G/C polymorphism and MD in an Iranian population. In this case-control association study, MD cases (N = 72) were recruited and were comprised of definitive MD (N = 58) and probable MD (N = 14) subjects. Normal healthy subjects (N = 100) were also included. Genotyping for MIF-173 G/C polymorphism was carried out using PCR-RFLP technique. There was a significant increase in genotype GG in patients with MD compared with the control group. (GG vs. GC + CC, P = 0.02, OR = 2.08, 95% CI: 1.02-4.3). This was more significant when definitive MD was stratified and compared with the controls (GG vs. GC + CC, P = 0.009, OR = 2.6, 95% CI = 1.19-6.18). This study's result indicates the potential role of MIF in MD of which further evaluation is required. Also, the more significant association between MIF gene polymorphism and definitive MD designates the involvement of specific pathogenic mechanisms which may be considered as a marker for diagnosis.
International Journal of Immunogenetics 04/2013; · 1.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: Subject: Survivin expression is correlated with tumor aggressiveness and severity in head and neck carcinoma. A polymorphism at position -31 (G/C) (rs 9904341) has been associated with cancer risk in several studies. We evaluated the correlation of this polymorphism with clinical manifestation of patients with tongue squamous cell carcinoma (SCC) in an Irananian population. Methods: Paraffin-embedded tissue sections from patients with tongue SCC (n=91) were evaluated for association between the survivin -31 (G/C) polymorphism and tumor staging, pathological grade, lymph node metastasis, tumor size, and recurrence of tumor. Results: There was a significant increase of presence of allele C in patients who were at stages III and IV compared to patients with lower stages [GC+CC vs. GG, p=0.025, odds ratio [OR] 2.76, 95% confidence interval [CI] [1.03-7.4]). In addition, presence of allele C was significantly decreased in patients with T1 tumor size compared to patients with larger tumor size (p=0.03, OR 0.6, 95% CI [0.2-2.03]). Conclusion: Presence of the C allele was significantly associated with tumor stage and size; therefore, survivin might be an important marker in the prognosis of tongue SCC that requires further investigation.
Genetic Testing and Molecular Biomarkers 11/2012; · 1.44 Impact Factor
[show abstract][hide abstract] ABSTRACT: Objective: Both adaptive and innate immune systems are involved in coronary artery disease (CAD). The aim of this study was to evaluate TH17 cytokines expression profiles in un-stimulated peripheral blood lymphocytes (PBMCs) of patients with coronary artery disease. Methods: Expression profiles of IL-17, IL-23, and TGF-β1 were determined in individuals with and without CAD using Real-time PCR. Results: A significant decrease in IL-23 gene expression in un-stimulated PBMCs of patients with CAD compared to those without CAD was found (p=0.003, OR=0.045, 95% CI: 0.006-0.355). Conclusion: Our data reinforce the potential role of the IL-23 as a critical regulatory molecule that bridges the innate and adaptive arms of the immune system in the complex mechanisms associated with the development of atherosclerosis.
[show abstract][hide abstract] ABSTRACT: To assess the expression of vascular endothelium growth factor (VEGF) mRNA in unstimulated peripheral blood mononuclear cells of patients with and without coronary artery disease (CAD). We also studied whether the functional VEGF -2,578C/A polymorphism may influence the level of VEGF mRNA expression in individuals undergoing coronary angiography because chest pain. We assessed 50 consecutive patients with angiographically confirmed CAD (CAD+). Also, 50 consecutive individuals with normal coronary studies were included in the study for comparison. VEGF mRNA expression was examined using quantitative real-time PCR and genotyping for VEGF -2,578C/A was performed using ARMS-PCR technique. VEGF mRNA expression was significantly decreased in CAD+ patients when compared to CAD- individuals (p = 0.01). The frequency of VEGF -2578 allele C and genotype CC was increased in CAD+ patients. In this regard, homozygosity for the CC genotype was more commonly observed in CAD+ (30 %) than in those without CAD disease (18 %). However, the difference was slightly out of the range of significance (p = 0.1). In addition, a trend for reduction in the expression of VEGF mRNA was observed when patients carrying the VEGF -2,578AA genotype were compared with those VEGF -2,578AC heterozygous or those homozygous for the VEGF -2,578CC genotype. VEGF gene expression is decreased in individuals with CAD+ disease. The VEGF -2,578C/A polymorphism may influences the expression of VEGF.
[show abstract][hide abstract] ABSTRACT: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is an autosomal recessive form of hypophosphatemia with hyperphosphaturia, hypercalciuria, and hypercalcemia. In two reports on six affected kindreds with HHRH, the disease was mapped to chromosome 9q34, which contains the SLC34A3 gene that encodes the renal type 2c sodium-phosphate cotransporter. Our objective was to define the clinical course of these cases in a family with HHRH and to screen for SLC34A3 gene in order to determine whether these mutations are responsible for HHRH.
After clinical and biochemical evaluations, the entire SLC34A3 gene was screened using PCR amplification followed by direct sequencing technique. In this paper, we describe a new kindred with HHRH and a case of progressive and complicated HHRH presenting at age 27 years.
We found 101-bp deletion in intron 9 of the SLC34A3 gene. The index patient was homozygous for this mutation which has been previously reported in a Caucasian population. This is the first report for presence of SLC34A3 intron 9 deletion in an Iranian population.
These data showed that HHRH can be easily missed or underdiagnosed. Genetic evaluation of patients with familial hypercalciuria, hypophosphatemia and nephrolithiasis is needed for further information on the prevalence and management of this rare disorder.
Journal of Clinical Research in Pediatric Endocrinology 06/2012; 4(2):89-93.
[show abstract][hide abstract] ABSTRACT: Activating mutations of potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11), which encodes Kir6.2 (beta-cell adenosine triphosphate-sensitive potassium [K(ATP)] channel subunit), have been associated with neonatal diabetes mellitus (NDM) in different studies. Treatment with oral sulfonylureas in place of exogenous insulin injections results in improved glycemic control in most patients carrying these mutations. Exploration of genetic causes of NDM occurring before the age of 6 months has been proposed as an important issue in identification of monogenic forms of diabetes, which might be critical in their therapeutic management, as a consequence.
Mutation screening of the KCNJ11 gene was carried out using PCR amplification followed by direct sequencing in three family members: the proband, ND1, diagnosed at 40 days of age (current age 7 years); his sibling, ND2, diagnosed at 2 years of age (current age 14 years); and their father, ND3, diagnosed at 15 years of age (current age 35 years), who had been exclusively treated with insulin. The effect of the E227K mutation was also examined in a homology model of Kir6.2.
Our results revealed the presence of the heterozygous missense mutation c. 679 G/A (E227K) in all three patients, who were all able to successfully transfer from insulin injections to an oral sulfonylurea, with improved glycemic control.
We found that three members of a family with highly variable age of onset of insulin-treated diabetes, diagnosed at 40 days, 2 years, and 15 years of age, all carried the E227K mutation in KCNJ11 and could switch to an oral sulfonylurea. This mutation has been previously reported in patients with permanent and transient NDM, as well as later-onset diabetes; this report adds to the variability in phenotypic presentation and further supports genetic testing in all diabetic members of any family affected by NDM.
[show abstract][hide abstract] ABSTRACT: Survivin expression is correlated with suppression of apoptosis in human solid tumors. A polymorphism at position -31 (G/C) (rs 9904341) has been associated with cancer risk in several studies. We evaluated the correlation of this polymorphism with the risk of papillary thyroid carcinoma (PTC) in an Irananian population. The cases consisted of patients with PTC (n=123) and normal controls, composed of non-related healthy people (n=131). The frequency of GC or CC genotype in patients with PTC was significantly higher than in the controls [GC+CC vs GG, p=0.02 OR; 1.7, 95%CI (1.05-3.04)]. There was a significant difference between patients with more aggressive clinical manifestations, including lymphatic involvement compared to the controls [GC+CC vs GG, p=0.0006, OR; 3.7, 95%CI (1.6-9.2)]. The presence of C allele was significantly associated with the presence of more profound manifestations, including lymph node involvement, vascular involvement and multifocality.
Pathology - Research and Practice 02/2012; 208(2):100-3. · 1.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: Apolipoprotein E (apo E) plays a major role in lipid metabolism, obesity and accordingly in development of diabetes and coronary heart disease (CHD). Our main objective was to evaluate the association between apo E gene polymorphism with anthropometric measures.
Participants were selected from zone 17 Tehran/Iran. We assessed height, weight, body mass index (BMI), waist circumference (WC), blood pressure, serum fasting blood sugar, total cholesterol and triglycerides. Genotyping for apo E gene polymorphism was carried out using PCR-RFLP technique.
Among total study population (n=311), 156 subjects were diabetic. The apo E3/E3 was the most common genotype in our population while E2 and E4 alleles had lower frequencies, respectively. After adjustment for diabetes, the apo E2 and E4 alleles were significantly associated with hypercholesterolemia and WC, respectively (p= 0.009, 0.034). This association was also related to sex and age. The probability of having abdominal obesity in E4 allele carriers was increased from 0.22 to 8.12 in women and to 3.08 in age ≥ 50 years.
Apo E polymorphism had significant influences on WC and total cholesterol level in patients with type 2 diabetes. This study highlights the importance of lifestyle modifications which may be more beneficial in hypercholesterolemic women carriers of E2 and E4 alleles concomitant central obesity.
Journal of diabetes and metabolic disorders. 01/2012; 11(1):18.
[show abstract][hide abstract] ABSTRACT: The protective effects of TGF-β have been documented in various autoimmune diseases, mostly in organ-specific autoimmunity including type 1 diabetes mellitus (T1DM). However, TGF-β also plays a role as a pro-inflammatory mediator by induction of Th17 cytokine production. IL-23 also plays a key role in differentiation of Th17 cells, which are implicated in pathogenesis of autoimmune conditions including T1DM. The aim of this study was to investigate and compare the difference in the level of TGF-β1 and IL-23 gene expression in unstimulated peripheral blood mononuclear cells (PBMCs) of patients with different forms of diabetes compared with normal healthy controls subjects. Patients with T1DM were grouped as early-onset T1DM (N = 20) with age at diagnosis <18 years and late-onset T1DM (N = 20) with the age at onset >18 years. Patients with T2DM (N = 20) and normal healthy controls (N = 20) were recruited from the same area. TGF-β1 and IL-23 gene expression in fresh unstimulated PBMCs was determined in each group using quantitative real-time PCR. The results confirmed that a significant difference in TGF-β1 and IL-23 gene expression was observed in both forms of juvenile-onset T1DM and adult-onset T1DM compared to the controls and T2DM patients. There was no significant difference for TGF-β gene expression in patients with T2DM and controls. We therefore conclude that our results support the previous data on TGF-β gene down-regulation in T1DM. Also up-regulation of IL-23 has been observed in T1DM whilst it was down-regulated in T2DM. We also found no significant difference between juvenile-onset and adult-onset T1DM indicating same mechanism might be involved in the pathogenesis of both types. More studies on different cytokines in Th17 pathways are required to further confirm our finding.
[show abstract][hide abstract] ABSTRACT: Survivin is an inhibitor of apoptosis protein, which is up-regulated in endometrial cancer (EC). A promoter region polymorphism (-31G/C) in the survivin gene has been reported as a modulator of gene expression. The aim of this study was to explore the frequency of survivin -31G/C polymorphism in tumor tissues from patients with EC in an Iranian population compared to that of healthy controls.
Paraffin-embedded tissue sections from patients diagnosed with EC (n = 31) and healthy controls (n = 30) were examined. Genotyping for survivin -31G/C polymorphism was performed using polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP).
The presence of allele C was found to be significantly increased in EC tissues compared to the healthy tissues (GG vs GC + CC, P = 0. 01; OR, 3.6; 95% CI, 1.1-11.9).
Our data are in keeping with a previous finding regarding the role of survivin gene polymorphism in malignancies. This finding highlights the role of survivin in pathogenesis of various carcinomas, which might have therapeutic implications.
International Journal of Gynecological Cancer 09/2011; 22(1):35-7. · 1.94 Impact Factor