Tamires Flauzino1, Daniela Frizon Alfieri1, Wildea Lice de Carvalho Jennings Pereira1,2, Sayonara Rangel Oliveira3, Ana Paula Kallaur1, Marcell Alysson Batisti Lozovoy1,3, Damacio Ramón Kaimen-Maciel4, Karen Brajão de Oliveira5, Andrea Name Colado Simão1,3, Edna Maria Vissoci Reiche6,7. 1. Laboratory of Applied Immunology, Health Sciences Center, University of Londrina, Londrina, Paraná, Brazil. 2. Outpatient Clinic for Neurology, University Hospital, State University of Londrina, Londrina, Paraná, Brazil. 3. Department of Pathology, Clinical Analysis and Toxicology, Health Sciences Center, University Hospital, State University of Londrina, Av. Robert Koch 60, Londrina, Paraná, CEP 86038-350, Brazil. 4. Hospital Santa Casa de Misericórdia de Londrina, Londrina, Paraná, Brazil. 5. Laboratory of Molecular Genetics and Immunology, Department of Pathological Sciences, Biological Sciences Center, State University of Londrina, Londrina, Paraná, Brazil. 6. Laboratory of Applied Immunology, Health Sciences Center, University of Londrina, Londrina, Paraná, Brazil. reiche@sercomtel.com.br. 7. Department of Pathology, Clinical Analysis and Toxicology, Health Sciences Center, University Hospital, State University of Londrina, Av. Robert Koch 60, Londrina, Paraná, CEP 86038-350, Brazil. reiche@sercomtel.com.br.
Abstract
OBJECTIVE: The aim of this study was to evaluate the association between rs3761548 FOXP3 (-3279 C > A) variant and multiple sclerosis (MS), disability, disability progression, as well as transforming growth factor (TGF)-β1 and interleukin (IL)-10 plasma levels in MS patients. METHODS AND SUBJECTS: The study included 170 MS patients and 182 controls. Disability was evaluated using Expanded Disability Status Scale (EDSS) and categorized as mild (EDSS ≤ 3) and moderate/high (EDSS > 3). Disability progression was evaluated using Multiple Sclerosis Severity Score (MSSS). The rs3761548 variant was determined with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Plasma levels of TGF-β1 and IL-10 were determined using immunofluorimetric assay. RESULTS: CA and AA genotypes were associated with MS [odds ratio (OR) 2.03, 95% confidence interval (CI) 1.66-3.53, p = 0.012; OR 8.19, 95% CI 3.04-22.07, p < 0.001, respectively). With the dominant model, the CA + AA genotypes were associated with MS (OR 2.57, 95% CI 1.50-4.37, p < 0.001). In the recessive model, the AA genotype was also associated with MS (OR 5.38, 95% CI 2.12-13.64, p < 0.001). After adjustment by age, ethnicity, BMI and smoking, all these results remained significant, as well as female patients carrying the CA + AA genotypes showed higher TGF-β1 than those carrying the CC genotype (OR 1.35, 95% CI 1.001-1.054, p = 0.043). No association was observed between the genotypes and disability, disability progression and IL-10 levels. CONCLUSION: These results suggest that the A allele of FOXP3 -3279 C > A variant may exert a role in the T regulatory cell function, which could be one of the factors involved in the susceptibility for MS in females.
OBJECTIVE: The aim of this study was to evaluate the association between rs3761548FOXP3 (-3279 C > A) variant and multiple sclerosis (MS), disability, disability progression, as well as transforming growth factor (TGF)-β1 and interleukin (IL)-10 plasma levels in MS patients. METHODS AND SUBJECTS: The study included 170 MS patients and 182 controls. Disability was evaluated using Expanded Disability Status Scale (EDSS) and categorized as mild (EDSS ≤ 3) and moderate/high (EDSS > 3). Disability progression was evaluated using Multiple Sclerosis Severity Score (MSSS). The rs3761548 variant was determined with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Plasma levels of TGF-β1 and IL-10 were determined using immunofluorimetric assay. RESULTS: CA and AA genotypes were associated with MS [odds ratio (OR) 2.03, 95% confidence interval (CI) 1.66-3.53, p = 0.012; OR 8.19, 95% CI 3.04-22.07, p < 0.001, respectively). With the dominant model, the CA + AA genotypes were associated with MS (OR 2.57, 95% CI 1.50-4.37, p < 0.001). In the recessive model, the AA genotype was also associated with MS (OR 5.38, 95% CI 2.12-13.64, p < 0.001). After adjustment by age, ethnicity, BMI and smoking, all these results remained significant, as well as female patients carrying the CA + AA genotypes showed higher TGF-β1 than those carrying the CC genotype (OR 1.35, 95% CI 1.001-1.054, p = 0.043). No association was observed between the genotypes and disability, disability progression and IL-10 levels. CONCLUSION: These results suggest that the A allele of FOXP3 -3279 C > A variant may exert a role in the T regulatory cell function, which could be one of the factors involved in the susceptibility for MS in females.
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