ABSTRACT
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.
Subject(s)
CD4-Positive T-Lymphocytes/drug effects , GTPase-Activating Proteins/genetics , Interleukin-2 Receptor alpha Subunit/genetics , Multiple Sclerosis/genetics , Receptors, Calcitriol/genetics , Vitamin D/pharmacology , Adult , CD4-Positive T-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/pathology , Female , GTPase-Activating Proteins/agonists , GTPase-Activating Proteins/blood , Gene Expression , Gene Expression Profiling , Genetic Predisposition to Disease , Humans , Interleukin-2 Receptor alpha Subunit/antagonists & inhibitors , Interleukin-2 Receptor alpha Subunit/blood , Male , Middle Aged , Multiple Sclerosis/blood , Multiple Sclerosis/pathology , Polymorphism, Single Nucleotide , Primary Cell Culture , Receptors, Calcitriol/blood , Response Elements , Vitamin D/bloodABSTRACT
BACKGROUND: Inconsistent results have been obtained with regard to headache comorbidity in multiple sclerosis (MS). OBJECTIVE: Investigate the one-year prevalence of migraine and tension-type headache (TTH) in Norwegian MS patients and relate this to clinical parameters. METHODS: A questionnaire concerning headache was administered to 756 MS patients and 1090 controls and used to determine the one-year prevalence of migraine and frequent TTH. RESULTS: No significant differences were seen between patients and controls or between patients with different disease course. Less migraine was observed in patients with Expanded Disability Status Scale score (EDSS) ≥4.0. CONCLUSIONS: This case-control study does not support an association between migraine or TTH and MS.
ABSTRACT
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.
Subject(s)
Multiple Sclerosis/epidemiology , Periodontitis/epidemiology , Smoking/epidemiology , Adult , Case-Control Studies , Comorbidity , Female , Humans , Male , Middle Aged , Norway/epidemiologyABSTRACT
OBJECTIVES: To better understand the interaction of antiepileptic drugs and production of sex hormones, possible effects of valproate (VPA), levetiracetam (LEV) and carbamazepine (CBZ) on steroidogenesis were investigated in the human adrenal carcinoma cell line H295R. MATERIALS AND METHODS: H295R cells were exposed to different concentrations of VPA, LEV or CBZ for 48 h. Sex hormone concentrations and mRNA expression levels were analyzed via radioimmunoassay and quantitative real time (RT)-PCR, respectively. RESULTS: In VPA-exposed cells estradiol levels decreased in a dose-dependent manner, while testosterone and progesterone levels were unaffected. Expression of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), steroidogenic acute regulatory protein (StAR), CYP11a, CYP17, CYP21, 3betaHSD2, 17betaHSD1 was downregulated and expression of CYP11beta2 was upregulated. No effect on sex hormone production was observed under influence of LEV or CBZ. Expression of StAR, CYP17, CYP19 and 3betaHSD2 was downregulated in LEV-exposed cells, and expression of HMGR, CYP11beta2 and CYP17 was downregulated in CBZ-exposed cells. CONCLUSIONS: VPA exposure resulted in a decrease in estradiol levels and a general downregulation of expression of genes encoding for enzymes early in steroidogenesis. No consistent changes were seen with LEV or CBZ exposure.