RESUMO
Multiple sclerosis (MS) is an inflammatory, demyelinating disorder of the central nervous system that develops in genetically susceptible individuals. The majority of the MS-associated gene variants are located in genetic regions with importance for T-cell differentiation. Vitamin D is a potent immunomodulator, and vitamin D deficiency has been suggested to be associated with increased MS disease susceptibility and activity. In CD4+ T cells, we have analyzed in vitro vitamin D responsiveness of genes that contain an MS-associated single-nucleotide polymorphism (SNP) and with one or more vitamin D response elements in their regulatory regions. We identify IL2RA and TAGAP as novel vitamin D target genes. The vitamin D response is observed in samples from both MS patients and controls, and is not dependent on the genotype of MS-associated SNPs in the respective genes.
Assuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Proteínas Ativadoras de GTPase/genética , Subunidade alfa de Receptor de Interleucina-2/genética , Esclerose Múltipla/genética , Receptores de Calcitriol/genética , Vitamina D/farmacologia , Adulto , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Feminino , Proteínas Ativadoras de GTPase/agonistas , Proteínas Ativadoras de GTPase/sangue , Expressão Gênica , Perfilação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Subunidade alfa de Receptor de Interleucina-2/antagonistas & inibidores , Subunidade alfa de Receptor de Interleucina-2/sangue , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Esclerose Múltipla/patologia , Polimorfismo de Nucleotídeo Único , Cultura Primária de Células , Receptores de Calcitriol/sangue , Elementos de Resposta , Vitamina D/sangueRESUMO
BACKGROUND AND PURPOSE: Periodontitis has been reported to be associated with several systemic disorders, and recently a possible relationship with multiple sclerosis (MS) was suggested. The aim of the present study was to investigate the association between periodontitis and MS in a Norwegian cohort. METHODS: A case-control study in 756 MS patients and 1090 controls was conducted, and logistic regression analysis, adjusting for age, gender, place of residence, mononucleosis and smoking, was performed to investigate the association between MS and periodontitis. RESULTS: In the unadjusted analysis a higher prevalence of periodontitis was seen in MS patients, but this difference was not statistically significant after adjusting for the covariates. CONCLUSIONS: The previously suggested association between MS and periodontitis is not supported in this study. Our results underline the importance of adjusting for relevant covariates in epidemiological research.