RESUMO
BACKGROUND: Several inflammatory mediators have been proposed to contribute to the pathogenesis of atherosclerosis. The aim of this study was to evaluate the quantitative expression of pro-inflammatory cytokines in un-stimulated peripheral blood mononuclear cell of patients with coronary artery disease (CAD). METHODS: Interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha, and interferon-gamma (IFN-γ) gene expression were evaluated in angiography confirmed patients with and without CAD in a case-control study using quantitative real-time polymerase chain reaction. RESULTS: A significant increase (P = 0.030) in IL-1ß gene expression was found in patients with CAD [median interquartile range (IQR) = 4.890 (6.084)] compared to patients without CAD [median (IQR) = 1.792 (3.172)]. Despite the increase in IFN-γ gene expression in patients with CAD [median (IQR) = 1.298 (3.896)] versus patients without CAD [median (IQR) = 0.841 (2.79)], there was not statistically significant difference (P = 0.990). CONCLUSION: Our results provide evidence for possible association between IL-1ß and development of atherosclerosis as a crucial cytokine that induce a network of signaling pathways. This finding if proved in future would suggest IL-1ß as a potent therapeutic target in CAD.
RESUMO
Adiponectin appears to play an important role in the development and progression of several obesity-related malignancies. Also, overexpression of survivin, an inhibitor of apoptosis protein, is associated with increased risk of cancers. The aim of this study was to investigate the association between two polymorphisms in the adiponectin gene and endometrial cancer (EC) risk. We also investigated whether epistasis between surviving and adiponectin gene polymorphisms are associated with EC risk in an Iranian population. The samples comprised formalin-fixed, paraffin-embedded tissue sections obtained from the archive of the pathology department, Imam-Khomeini Hospital and Firouzgar hospital. After DNA extraction the genotyping was performed using PCR-RFLP technique. Single nucleotide polymorphisms (SNPs) in adiponectin (rs1063539, rs2241766) and survivin (rs9904341) gene were evaluated in the study. The increased frequency of ADIPOQ rs1063539C allele (CC+CG genotype) was associated with decreased EC risk [OR: 0.39(0.17-0.90)]. Survivin rs9904341C allele (CC+CG genotype) was associated with increased EC risk [crude OR: 2.75(1.27-5.95), adjusted OR: 2.93(1.27-6.76)]. We observed an epistatic interaction between survivin rs9904341 CC+CG genotype and ADIPOQ rs1063539 GG genotype increasing the risk of EC compared to those with other genotypes [OR: 4.86(1.88-12.54), P=0.001]. Our findings indicate that adiponectin might have a modulatory effect on survivin role and function in EC, which requires further investigation.
Assuntos
Adiponectina/genética , Neoplasias do Endométrio/genética , Epistasia Genética , Proteínas Inibidoras de Apoptose/genética , Polimorfismo Genético , Idoso , Estudos Transversais , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Risco , SurvivinaRESUMO
Several studies have shown the correlation between RANTES gene and inflammatory disorders; the aim of the present study was to investigate the association between RANTES promoter gene polymorphism and Meniere's disease (MD) in an Iranian population. In this study patients with MD comprising definite MD (N = 56) and probable MD (N = 15) were selected according to diagnostic criteria of AAO-HNS. The control group (N = 101) were healthy normal subjects who did not have a history of ear disease and vertigo. PCR-RFLP for RANTES -403G>A has been performed. We found a protective role for RANTES -403A allele in male group in our population. None of the male patients with MD were carrier of allele A which was significantly different from the presence of allele A in the male control group (AA+GA vs. GG: p = 0.0004, OR 0.05, 95 % CI 0.001-0.39). This difference was not significant in female group. There was no significant association between RANTES gene polymorphism and the level of hearing loss. our results showed a sex-specific association between RANTES gene polymorphism and MD but more studies are necessary to further assess this association.
Assuntos
Quimiocina CCL5/genética , Doença de Meniere/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Humanos , Irã (Geográfico) , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Regiões Promotoras Genéticas , Fatores SexuaisRESUMO
Subject & Aim. Endothelial nitric oxide synthase (eNOS) is one of the most important candidate genes in CAD. A functional polymorphism within eNOS gene is a 27 bp VNTR on its intron 4 which has been shown to be associated with various diseases. In this study we investigated eNOS VNTR polymorphism in addition to eNOS gene expression profile in patients with CAD. Material and Methods. The study comprised patients with angiographically confirmed CAD (CAD(+)) and individuals with normal coronary as CAD(-). eNOS VNTR polymorphism frequencies were determined in both groups. In addition eNOS gene expression profile was examined using a quantitative real-time PCR. Results. We have found that aa genotype was significantly increasing the risk of CAD in our patients (aa versus ab + bb, P = 0.02, OR = 3.5; 95% CI: = 0.98 to 16.2). The differences in eNOS expression were not significant between patients and normal group; however in CAD(+) patients eNOS expression was higher than the expression level of patients carrying other genotypes (P = 0.16). Conclusion. We have observed that eNOS gene polymorphism was associated with CAD in angiography-confirmed patients. However, the difference in eNOS gene expression was not statistically significant between patients and control which might be due to the contribution of other confounding factors which require further investigations.
RESUMO
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.
Assuntos
Carcinoma de Células Escamosas/genética , Proteínas Inibidoras de Apoptose/genética , Polimorfismo Genético , Neoplasias da Língua/genética , Língua/patologia , Adulto , Idoso , Alelos , Carcinoma de Células Escamosas/patologia , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Survivina , Língua/metabolismo , Neoplasias da Língua/patologiaRESUMO
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-ß1 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.
Assuntos
Doença da Artéria Coronariana/imunologia , Regulação para Baixo , Interleucina-23/genética , Linfócitos/imunologia , Idoso , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Feminino , Humanos , Interleucina-17/genética , Interleucina-17/metabolismo , Interleucina-23/metabolismo , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Transcrição Gênica , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismoRESUMO
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Assuntos
Raquitismo Hipofosfatêmico Familiar/genética , Deleção de Genes , Hipercalciúria/genética , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIc/genética , Adulto , Sequência de Bases , Criança , Análise Mutacional de DNA , Raquitismo Hipofosfatêmico Familiar/complicações , Saúde da Família , Feminino , Predisposição Genética para Doença/genética , Humanos , Hipercalciúria/complicações , Íntrons/genética , Masculino , Dados de Sequência Molecular , LinhagemRESUMO
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.
Assuntos
Doença da Artéria Coronariana/genética , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Idoso , Alelos , Doença da Artéria Coronariana/metabolismo , Feminino , Expressão Gênica , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Assuntos
Diabetes Mellitus/diagnóstico , Diabetes Mellitus/genética , Mutação , Canais de Potássio Corretores do Fluxo de Internalização/genética , Adolescente , Adulto , Criança , Pré-Escolar , Diabetes Mellitus/tratamento farmacológico , Família , Hemoglobinas Glicadas/metabolismo , Heterozigoto , Humanos , Ligação de Hidrogênio , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Lactente , Masculino , Modelos Moleculares , Mutação de Sentido Incorreto , Canais de Potássio Corretores do Fluxo de Internalização/química , Domínios e Motivos de Interação entre Proteínas , Estrutura Quaternária de Proteína , Compostos de Sulfonilureia/administração & dosagem , Compostos de Sulfonilureia/uso terapêuticoRESUMO
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.
Assuntos
Proteínas Inibidoras de Apoptose/genética , Polimorfismo Genético , Neoplasias da Glândula Tireoide/genética , Adulto , Carcinoma , Carcinoma Papilar , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Irã (Geográfico) , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Medição de Risco , Fatores de Risco , Survivina , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/patologiaRESUMO
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
RESUMO
OBJECTIVE: 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. MATERIALS AND METHODS: 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). RESULTS: 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). CONCLUSION: 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.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias do Endométrio/genética , Proteínas Inibidoras de Apoptose/genética , Polimorfismo de Fragmento de Restrição , Idoso , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Estudos de Casos e Controles , Feminino , Humanos , Irã (Geográfico) , Pessoa de Meia-Idade , SurvivinaRESUMO
The protective effects of TGF-ß have been documented in various autoimmune diseases, mostly in organ-specific autoimmunity including type 1 diabetes mellitus (T1DM). However, TGF-ß 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-ß1 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-ß1 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-ß1 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-ß gene expression in patients with T2DM and controls. We therefore conclude that our results support the previous data on TGF-ß 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.
Assuntos
Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Regulação da Expressão Gênica , Interleucina-23/metabolismo , Leucócitos Mononucleares/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Adolescente , Adulto , Idade de Início , Idoso , Criança , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 2/imunologia , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto JovemRESUMO
OBJECTIVE: Klotho has an important role in development of coronary artery (CAD) disease. A functional variant of klotho gene (kl-vs) has been found as an independent risk factor for early-onset occult coronary artery disease (CAD) in previous studies. The Frequency of this variant was not known in Iranian population. We have examined the allele frequency of the kl-vs variant in a case-control study in an Iranian population. METHODS AND RESULTS: Genotyping for kl-vs variant was carried out in N=107 individuals including N=54 cases and N=53 control who all underwent coronary angiogram for CAD evaluation. Patients with >50% stenosis in vessels considered as case groups (or CAD
Assuntos
Doença da Artéria Coronariana/genética , Glucuronidase/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Irã (Geográfico) , Proteínas Klotho , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNARESUMO
OBJECTIVE: Increased RANTES expression has been described to have a role in atherosclerosis plaque formation. Functional polymorphisms within RANTES promoter region have shown association with increased risk of coronary atherosclerosis (CAD). The aim of this study was to examine the RANTES mRNA expression in patients with CAD compared to patients without CAD and its association with RANTES -403 G/A polymorphism in an Iranian population. METHODS: The study was performed on 319 patients who underwent coronary artery angiography and patients with >50% stenosis in vessels considered as case groups (CAD+) N=191 and normal vessels group as control (CAD-) N=128. In each group 20 patients were examined for RANTES mRNA expression. RANTES mRNA expression was examined using quantitative real-time PCR. Genotyping of -403 polymorphism was performed using PCR-RFLP technique. RESULTS: We found that RANTES mRNA expression was increased to 1.37 fold in CAD patients compared to the controls but the difference was not statistically significant. Also comparing the RANTES mRNA expression in patients with different RANTES -403 G/A polymorphism showed that in patients carrying AA genotype RANTES mRNA expression was increased to 1.74 fold compared to patients carrying GG genotype and to 1.51 fold compared to patients carrying GA genotype. No significant difference for allele and genotype frequencies of RANTES -403 polymorphism was found between cases and controls. CONCLUSION: More studies on larger number of samples are required to further evaluate role of RANTES in pathogenesis of CAD.
Assuntos
Quimiocina CCL5/genética , Doença da Artéria Coronariana/genética , Expressão Gênica , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Adulto , Idoso , Alelos , Feminino , Frequência do Gene , Genótipo , Humanos , Leucócitos Mononucleares/metabolismo , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Both genetic and environmental factors seem to play role in the etiology of Meniere's disease (MD). Several genes may be involved in susceptibility of MD including Human Leukocyte Antigens (HLA). The associations between MD and HLA alleles have been previously studied in other populations and certain HLA alleles were shown to be predisposing. The aim of this study was to determine the association between HLA-C allele frequencies and definite MD in patients who refer to Amir-Alam otolaryngology tertiary referral center in Tehran. Patients with definite MD (N=22) enrolled according to the diagnostic criteria of American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS). Cases with all 3 symptoms of MD (Vertigo, Tinnitus and lower frequency of sensory-neural hearing loss) were included and those with suspected MD were excluded from study. HLA-Cw allele frequencies were determined in patients non-related healthy controls (N=91) using PCR -SSP. We found that the frequency of HLACw*04 was significantly higher in patients compared to the controls [P = 0.0015, OR; 20, 95% CI (3.7-196.9)]. Our results revealed that HLA-C is a genetic predisposing factor in definite MD in patients who refer to Amir-Alam otolaryngology tertiary referral center.
Assuntos
Alelos , Antígenos HLA-C/genética , Doença de Meniere/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Frequência do Gene , Humanos , Lactente , Masculino , Doença de Meniere/etiologia , Doença de Meniere/imunologia , Pessoa de Meia-IdadeRESUMO
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). METHODS: The study group comprised of type 2 diabetes patients with (N=247) and without (N=241) DFU. Healthy control subjects (N=98) were also recruited from the same area. The ARMS-PCR technique was applied for genotyping of VEGF gene SNPs at positions -7*C/T and -2578*C/A. RESULTS: The frequency of genotype AA was significantly decreased in patients with DFU compared with diabetic subjects without DFU (AA vs CA+CC, p=0.003, OR=0.44, CI=0.24-0.80). Also there was a significant decrease in frequency of A allele in patients with DFU compared to the controls (p=0.02, OR=0.68, CI=0.48-0.96). CONCLUSION: It seems that lower frequency of A allele in patients with DFU is conferring a protective effect which might be as a result of increased angiogenesis in patients carrying this allele.
Assuntos
Pé Diabético/genética , Polimorfismo Genético , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Pé Diabético/epidemiologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
UNLABELLED: SUBJECT AND AIMS: Endothelial derived nitric oxide (eNOS) is involved in several functions playing important role in development of type 2 diabetes and insulin resistance. The aim of this study was to examine the association between eNOS intron 4 VNTR polymorphism and type 2 diabetes in an Iranian population. METHODS: A total of 220 patients with type 2 diabetes and 96 healthy control subjects were recruited from the same area. Genotyping was performed using PCR. RESULTS: A significant difference was found in genotype frequencies of eNOS polymorphism between patients and controls (aa+ab vs. bb p=0.02, OR 2.0 95% CI; 1.05-3.96). Also allele a frequency was significantly increased in patients with diabetes compared with controls (p=0.007, OR 2.1 95% CI; 1.19-4.08). We found that in patients with diabetic neuropathy the frequency of 'a' allele was significantly increased compared to the controls p=0.03, OR=1.8 95% CI (1.00-3.7). Both genotype and allele frequencies were significantly different between patients who were complication free compared to the controls [aa+ab vs. bb p=0.007, OR=2.6 95% CI (1.2-5.8) and p=0.001, OR=2.8 95% CI (1.4-5.9)] respectively with the a allele conferring the risk. CONCLUSION: The association between eNOS VNTR polymorphism and T2DM seems to be stronger in patients without diabetic complications indicating diverse effect of eNOS polymorphism on diabetes and diabetic microvascular complications.
Assuntos
Complicações do Diabetes/genética , Diabetes Mellitus Tipo 2/genética , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo Genético , Adulto , Idoso , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Feminino , Frequência do Gene , Genótipo , Humanos , Íntrons , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Repetições MinissatélitesRESUMO
BACKGROUND: A functional polymorphism in the uncoupling protein 2 (UCP2) gene promoter has been associated with obesity and type 2 diabetes (T2D) in some populations. The impact of UCP2 polymorphisms on diabetes and obesity is still under debate. Contradictory results have been reported in different populations world-wide. To clarify the contribution of the UCP2 gene -866 G/A polymorphism in the Iranian population, we studied its association with obesity and T2D. METHODS: A total of 225 unrelated subjects were studied: 75 T2D patients without obesity, 75 obese patients without diabetes and 75 control subjects. The UCP2 -866 G/A polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: In the normal Iranian population, GG polymorphism was significantly associated with an increased HDL-C level (P=0.027). G/A polymorphism was not associated with obesity and T2D in our study population, but the odds ratio (OR) between GG and G/A polymorphism was 0.61 with a confidence interval (CI) range of 0.34 - 1.08 in obese patients. Subjects with AA genotypes in all of the studied groups showed a lower body mass index (BMI) than subjects with the GG genotype. CONCLUSION: Although the data in our study population is not statistically significant, the A allele in the UCP2 gene promoter seems to be protective against obesity. This may suggest the possibility of UCP2 as a target molecule for studies on the etiology and treatment of obesity.
Assuntos
Diabetes Mellitus Tipo 2/genética , Canais Iônicos/genética , Proteínas Mitocondriais/genética , Obesidade/genética , Adulto , Idoso , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Proteína Desacopladora 2 , Adulto JovemRESUMO
OBJECTIVE: Papillary thyroid carcinoma (PTC) is the most frequent types of thyroid malignancies. Several genes may be involved in susceptibility of thyroid cancer including Human Leukocyte Antigens (HLA). The association of thyroid carcinoma with HLA alleles has been previously studied in other populations and certain HLA alleles were shown to be either predisposing or protective. The aim of this study was to determine the association between HLA-DR and papillary thyroid carcinoma in an Iranian population. DESIGN: HLA-DR antigen frequencies were determined in patients with papillary thyroid carcinoma (N=70) and non-related healthy controls (N=180) using PCR -SSP. MAIN OUTCOME: We found that HLA-DRB1*04 frequency was significantly higher in our patients compared to the controls [P=0.02, OR; 1.9, 95% CI (1.04-3.57)]. CONCLUSIONS: Our results revealed HLA-DRB1*04 as predisposing factor in papillary thyroid carcinoma in Iranian population. This confirms the previous findings for associations between HLA-DRB1 and differentiated carcinomas in other populations.