RESUMEN
BACKGROUND: Familial Mediterranean fever (FMF) is common in Azari-Turkish people, one of the biggest ethnic groups in Iran. In this study, we sought to investigate the mutation spectrum of the MEFV gene and any genotype-phenotype correlations. METHODS AND MATERIALS: 400 unrelated Azari-Turkish FMF patients were analyzed in this study. Mutations in exons 2, 3, 5, and 10 of the MEFV gene were investigated using direct Sanger sequencing, and their correlations with the clinical features of the patients were analyzed. RESULTS: At least one mutation was detected in 248 (62%) patients. The most common mutations were M694V (26.25%) and E148Q (24.75%), respectively. Abdominal pain (65.2%) and fever 204 (51%) were the most frequent clinical problems in all subjects. The analysis recognized a novel missense mutation in the coding region of the MEFV gene, named P313H, which is the first report of a new mutation in exon 2 of the MEFV gene in an Azari-Turkish family. CONCLUSION: Genotype-phenotype correlations obtained from this study would be helpful in the diagnosis and management of FMF patients in clinical situations. This novel missense mutation may provide useful evidence for further studies of FMF pathogenesis.
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Fiebre Mediterránea Familiar/genética , Predisposición Genética a la Enfermedad , Mutación Missense , Pirina/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , Fiebre Mediterránea Familiar/epidemiología , Fiebre Mediterránea Familiar/patología , Femenino , Estudios de Seguimiento , Estudios de Asociación Genética , Humanos , Irán/epidemiología , Masculino , Persona de Mediana Edad , Fenotipo , Pronóstico , Turquía/etnología , Adulto JovenRESUMEN
OBJECTIVE: Behçet's disease (BD) is a chronic multi-factorial inflammatory disease with the important role of genetic in activation of its inflammatory response. Interleukin (IL)-33 is a member of the IL-1 family of cytokines that affects innate and adaptive immune systems to promote inflammatory responses. In the current study, we investigated the association of IL-33 gene rs1342326 polymorphism and expression levels of this gene in peripheral blood mononuclear cells (PBMCs) with the susceptibility to BD in Azari population of Iran. METHODS: We recruited 44 patients with BD and 61 age and sex-matched healthy controls in this cross-sectional study. The existence of rs1342326 T/G IL-33 gene single nucleotide polymorphism was investigated using Tetra-Amplification Refractory Mutation System (Tetra-ARMS)-PCR. Allele and genotype distributions were evaluated among groups using chi-square or Fisher's test. Moreover, the mRNA levels of IL-33 in PBMCs were assessed through the Real-time PCR. RESULTS: Patients with BD exhibited a significantly higher prevalence of the T/G genotype of rs1342326 polymorphism compared with the control group. Moreover, the expression level of IL-33 in PBMCs was significantly higher in the BD group compared to the healthy controls. Interestingly, the rs1342326 T/G polymorphism was associated with higher IL-33 expression in patients with BD. There was no association between the clinical manifestation of BD and disease activity with rs1342326 polymorphism and IL-33 expression. CONCLUSIONS: Our study implies that rs1342326 T/G polymorphism of the IL-33 gene may contribute to the genetic susceptibility to BD in part through regulation of the IL-33 expression.
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Síndrome de Behçet/genética , Predisposición Genética a la Enfermedad , Interleucina-33/genética , Adulto , Síndrome de Behçet/sangre , Síndrome de Behçet/inmunología , Estudios de Casos y Controles , Estudios Transversales , Femenino , Frecuencia de los Genes , Humanos , Interleucina-33/inmunología , Interleucina-33/metabolismo , Irán , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/inmunologíaRESUMEN
INTRODUCTION: Epigenetic discusses to inherited changes in mitosis and meiosis in the gene expression pattern which is independent of primary DNA sequence. Since, SOCS1 hyper-methylation can activate JAK / STAT signaling pathway and activation of this pathway can directly affect the impact of different cytokines on cell function and subsequently lead to pathophysiology of diseases, in particular autoimmune diseases that interact directly with the amount of cytokines and due to the fact that the cause and pathology of Behcet's disease (BD) have not ever been completely determined. So, the purpose of this study was to evaluate the methylation pattern of SOCS1 gene in patients with BD and compare them with healthy group. METHODOLOGY: This study was a case-control study in which 50 patients with BD and 60 subjects as healthy group participated. Blood samples were collected from all participants and then Peripheral Blood Mononuclear Cells (PBMCs) were isolated through Ficoll method. After extraction of DNA by Salting out method and its analysis with Nano-drop, the methylation level of SOCS1 was examined using qMS-PCR technique. RESULTS: Findings about methylation and gene expression in SOCS1 gene showed that the level of SOCS1 methylation was increased in patient groups compared with healthy subjects (control group) which the increase was statistically significant (p-value<0.05). Also, the results of gene expression revealed that the fold change of SOCS1 gene expression was decreased in patient group compared with healthy subjects which the decrease was statistically significant (p-value<0.05). DISCUSSION AND CONCLUSION: According to the results of this study, it can be suggested that the DNA methylation of SOCS1 gene is likely to affect the gene expression and thereby contribute to the pathogenesis of Behcet's disease.
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Síndrome de Behçet/metabolismo , Metilación de ADN , Leucocitos Mononucleares/metabolismo , Proteína 1 Supresora de la Señalización de Citocinas/metabolismo , Adulto , Anciano , Síndrome de Behçet/genética , Síndrome de Behçet/patología , Estudios de Casos y Controles , Citocinas/genética , Citocinas/metabolismo , Femenino , Humanos , Leucocitos Mononucleares/patología , Masculino , Persona de Mediana Edad , Proteína 1 Supresora de la Señalización de Citocinas/genéticaRESUMEN
BACKGROUND: Interleukin 10 (IL-10) is a cytokine with potent anti-inflammatory properties that play a fundamental role in restrictive host immune response to pathogens, by means of that is a crucial importance for chronic inflammatory disease studies. Therefore, the goal of this study was to measure the correlation of the IL-10 gene polymorphisms with the susceptibility to Behçet's disease compared with the control group in the Azeri population and to determine the expression of this gene in the two groups. Also, real-time PCR was performed for evaluate the IL-10 mRNA expression of the associated polymorphisms. METHODS: In this study, blood samples from 47 (1 missed) patients and 58 (3 missed) healthy control were taken, and then mononuclear cells isolated with ficoll protocol. The DNA and RNA were subsequently extracted. They were examined for -592A/C (rs1800872) of IL-10 gene single nucleotide polymorphism (SNP) using RFLP-PCR. Allele and genotype distributions were evaluated among groups using chi-square or Fisher's test. Following this, the extracted RNA was converted to cDNA using the RT-PCR method, after that expression of IL-10 evaluated by Real-time PCR. Serum levels of IL-10 were measured using Enzyme-linked immunosorbent assay (ELISA). RESULTS: Rates of the rs1800872 A allele was statistically lower in the control group compared with BD patients (pâ¯=â¯0.0315 and ORâ¯=â¯1.90 (1.05-3.42)). Also, as we expected, the expression level of the IL-10 gene was seen to significantly decrease in the patient group compared to the control. CONCLUSIONS: Our study showed that the rs1800872 A allele of the IL-10 gene may contribute to the genetic susceptibility of BD by regulating the expression of IL-10. Also as we expected, the expression level of this gene was seen to significantly decrease in the patient group compared to the control.
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Alelos , Síndrome de Behçet/inmunología , Predisposición Genética a la Enfermedad , Interleucina-10/genética , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Síndrome de Behçet/genética , Femenino , Humanos , Interleucina-10/inmunología , Masculino , Persona de Mediana EdadRESUMEN
Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a periodic fever syndrome inherited in an autosomal dominant fashion. It stems from mutations in the TNFRSF1A (accession number: NM_001065) gene expressing the receptor for tumor necrosis factor α. A patient with TRAPS may present with prolonged episodes of fever attacks, abdominal pain, severe myalgia, and painful erythema on the trunk or extremities. Here, we report an 8-year-old boy with febrile attacks occurring every 1-2months and continuing for 3-4days. The patient experienced 40°C-fever attacks without chills. Approximately 80% of fever attacks were accompanied by abdominal manifestations. Direct sequencing analysis was used to assess the genomic DNA of the patient, and a heterozygous R426L mutation in exon 10 of the TNFRSF1A gene in an autosomal dominant inheritance fashion was identified. Further genetic analyses were also carried out on his parents. Due to the fact that the mutation was not inherited from the parents, it was likely that R426L was a de novo and novel mutation in the TNFRSF1A gene, which can trigger TRAPS or TRAPS-like symptoms.
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Fiebre/genética , Enfermedades Autoinflamatorias Hereditarias/genética , Heterocigoto , Mutación Missense , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Sustitución de Aminoácidos , Niño , Humanos , Masculino , SíndromeRESUMEN
BACKGROUND: Behcet's Disease (BD) is a chronic systemic inflammatory disease of unknown etiology, principally characterized by relapsing periods of a broad range of clinical symptoms. Cytokines play fundamental roles in the pathogenesis of BD. Polymorphisms within cytokine genes have been found to play a pathogenic role in the development of autoimmune/inflammatory disorders. Interleukin 27 (IL-27), a new pro-/anti-inflammatory cytokine, is a great candidate for chronic inflammatory disease studies. The purpose of this study was to investigate a possible association between polymorphisms in the IL-27 gene and susceptibility to BD. METHODS: Fifty Iranian patients with BD and one hundred healthy individuals were examined for rs153109A/G and rs181206T/C IL-27 gene single nucleotide polymorphisms using RFLP-PCR and ARMS-PCR, respectively. Allele and genotype distributions were compared between groups using chi-square or Fisher's exact test. RESULTS: Frequencies of the rs153109AA genotype and rs153109A allele were statistically higher in BD patients compared with the control group (p = 0.034 and p = 0.011, respectively). The genotype and allele frequencies of rs181206 T/C polymorphism in BD patients were not significantly different from those of healthy controls. CONCLUSIONS: Present findings demonstrate for the first time that the IL-27 gene rs153109 A/G SNP may be involved in susceptibility to BD in the Iranian population.
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Síndrome de Behçet/genética , Predisposición Genética a la Enfermedad , Interleucinas/genética , Polimorfismo de Nucleótido Simple , Adulto , Femenino , Genotipo , Humanos , MasculinoRESUMEN
BACKGROUND: This study was conducted to determine the effect of fish oil (FO) supplements on high density lipoprotein cholesterol (HDL-C), apolipoprotein-AI (Apo-AI), malondialdehyde (MDA), arylesterase (Aryl), and paraoxonase-1 (PON1) activity in female patients with rheumatoid arthritis (RA). METHODS: A total of 90 RA patients were randomly allocated into two groups that were treated with one FO pearl (1 gr) daily or placebo for three months in addition to conventional treatment. HDL-C, Apo-AI, and MDA levels as well as PON1 and Aryl activities were measured before and after treatment. Independent t-test was used to match basal parameters of case and control groups. Paired t-test was used to assess significance of the differences. Correlation was evaluated by Pearsons test and the statistical significance was set at P < 0.05. RESULTS: No significant differences were noted between FO and placebo patients with regards to age, disease duration, post-menopausal status, conventional therapy, body mass index (BMI), and numbers of swollen and tender joints at the beginning of the study. There were 83 patients who completed the three-month follow up. Serum levels of HDL-C (P = 0.018), Apo-AI (P = 0.165), Aryl (P = 0.026), and PON1 (P = 0.049) activity increased, whereas MDA levels decreased significantly with FO supplementation (P = 0.077). Significant correlations between increased PON1 activity and both HDL-C (P = 0.007, r = 0.419) and Apo-AI (P < 0.001, r = 0.742) concentrations as well as between HDL-C and Apo AI levels (P = 0.01, r = 0.403) were found. CONCLUSION: According to the results of this study, FO could increase serum HDL-C and PON1 levels and Aryl activity in female patients with RA.
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Artritis Reumatoide/dietoterapia , Arildialquilfosfatasa/sangre , Suplementos Dietéticos , Aceites de Pescado/uso terapéutico , Adolescente , Adulto , Anciano , Apolipoproteína A-I/sangre , Artritis Reumatoide/sangre , Artritis Reumatoide/complicaciones , Artritis Reumatoide/enzimología , Aterosclerosis/etiología , Aterosclerosis/prevención & control , Biomarcadores/sangre , Hidrolasas de Éster Carboxílico/sangre , HDL-Colesterol/sangre , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Malondialdehído/sangre , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Genetic factors that predispose individuals to Behcet's disease (BD) are considered to play an important role in the development of the disease. The serum level of tumor necrosis factor (TNF) is elevated in patients with BD, and a dramatic response to anti-TNF-alpha antibody treatment further supports the role of TNF in BD. We investigated the distribution of TNF-alpha promoter -1031T/C and -308G/A polymorphisms in 53 BD patients of Iranian Azeri Turks and 79 matched healthy controls, via the PCR-RFLP technique. The frequency of the TNF-alpha -1031C allele was significantly higher in Behcet's patients than in healthy controls (p < 0.0001, OR = 3.08; 95% CI = 1.73-5.47), whereas the frequency of the TNF-alpha -308A allele was similar in the two compared groups. The frequency of CG haplotype was significantly higher (p < 0.0001, OR = 3.42; 95% CI = 1.89-6.18), and that of the TA haplotype was significantly lower in BD patients than in healthy controls. These results suggest that TNF-alpha is a susceptibility gene for BD in patients from Iranian Azeri Turk ethnic group.
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Síndrome de Behçet/genética , Predisposición Genética a la Enfermedad , Polimorfismo Genético , Factor de Necrosis Tumoral alfa/genética , Adulto , Síndrome de Behçet/epidemiología , Femenino , Frecuencia de los Genes , Haplotipos , Humanos , Irán/epidemiología , Masculino , Polimorfismo de Nucleótido Simple , Regiones Promotoras GenéticasRESUMEN
The objective of this study was to compare the prevalence of musculoskeletal complaints and rheumatic disorders in Caucasians and Turks in an identical environment. Subjects were selected randomly for an interview from Tehran's 22 districts. The Community Oriented Program for Control of Rheumatic Diseases questionnaire was filled in, positive cases were examined, and if needed, laboratory or X-ray tests were performed. A total of 4,096 houses were visited, and 10,291 persons were interviewed. They were 71.4% Caucasians and 23.1% Turks with similar distribution of age and gender. Musculoskeletal complaints of the past 7 days were detected in 40.8% of Caucasians and 45.5% of Turks (p < 0.001). In Caucasians, the total of musculoskeletal complaints in men was 33.8% (95% CI, 31.4-36.2%) versus 48.3% in women (95% CI, 45.7-50.8%). In Turks, the total of musculoskeletal complaints in men was 36.6% (95% CI, 32.2-41.1%) versus 55.8% in women (95% CI, 55.8-60.6%). The data of Caucasians versus Turks were as follows: knee pain 20.2% (95% CI, 18.2-22.1) versus 24.1% (95% CI, 20.5-27.6), with p < 0.001; dorso-lumbar spine pain 15.1% (95% CI, 13.6-16.6) versus 18.4% (95% CI, 15.1-21.8), with p < 0.001; shoulder pain 10.7% (95% CI, 9.4-11.9) versus 12.3% (95% CI, 9.7-14.8), with p = 0.025; osteoarthritis 14.1% (95% CI, 12.8-15.2) versus 16.4% (95% CI, 14.3-18.6), p = 0.04; and knee osteoarthritis 12.3% (95% CI, 11.8-14.1) versus 15.3% (95% CI, 13.3-17.4), with p < 0.001). There were no significant differences regarding the prevalence of soft tissue rheumatism, rheumatoid arthritis, ankylosing spondylitis, Behcet's disease, fibromyalgia, and gout. Although musculoskeletal complaints were more frequent in Turks than in Caucasians, the prevalence of rheumatic disorders was rather similar except for knee osteoarthritis.
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Encuestas Epidemiológicas , Enfermedades Reumáticas/etnología , Salud Urbana/estadística & datos numéricos , Población Urbana , Población Blanca/etnología , Adolescente , Adulto , Distribución por Edad , Anciano , Femenino , Humanos , Irán/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Encuestas y Cuestionarios , Turquía/etnología , Adulto JovenRESUMEN
OBJECTIVE: To find the prevalence of musculoskeletal complaints and rheumatic disorders in Iran. METHODS: Tehran, with one-ninth of the population of Iran and of mixed ethnic origins, was selected as the field. Subjects were randomly selected from the 22 districts. Interviews were conducted once a week, on the weekend. The 3 phases of stage 1 were done on the same day, in parallel, like the fast-track Community Oriented Program for Control of Rheumatic Diseases (COPCORD). RESULTS: Four thousand ninety-six houses were visited and 10,291 persons were interviewed. Musculoskeletal complaints during the past 7 days were detected in 41.9% of the interviewed subjects. The distribution was: shoulder 14.5%, wrist 10%, hands and fingers 9.4%, hip 7.1%, knee 25.5%, ankle 9.8%, toes 6.1%, cervical spine 13.4%, and dorsal and lumbar spine 21.7%. Degenerative joint diseases were detected in 16.6% of subjects: cervical spondylosis 1.8%, knee osteoarthritis (OA) 15.3%, hand OA 2.9%, and hip OA 0.32%. Low back pain was detected in 15.4% and soft tissue rheumatism in 4.6%. Inflammatory disorders were rheumatoid arthritis 0.33%, seronegative spondyloarthropathies 0.23%, ankylosing spondylitis 0.12%, systemic lupus erythematosus 0.04%, and Behçet's disease 0.08%. Fibromyalgia was detected in 0.69% and gout in 0.13% of the studied population. CONCLUSION: The large urban COPCORD study in Iran showed a high prevalence of rheumatic complaints in the population over the age of 15 years, 41.9%. Knee OA and low back pain were the most frequent complaints.
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Encuestas Epidemiológicas , Enfermedades Reumáticas/epidemiología , Adolescente , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Irán/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Población UrbanaRESUMEN
This study was conducted to determine the prevalence of oral aphthosis in a normal population in Iran, using the data of the WHO-ILAR COPCORD study in Iran. We conducted this study in Tehran, the capital of Iran which was selected as the COPCORD study field. In 22 districts of Tehran, 50 clusters were randomly selected. Of the selected houses, 4,096 households were visited and 10,291 persons were interviewed (response rate of 75%). Out of the 10291 subjects interviewed, 2592 had aphthous ulcers which translated to a prevalence of 25.2% (95% confidence interval: 24.4% to 26.0%). The prevalence of oral aphthosis was rather high in this normal population.