ABSTRACT
BACKGROUND: Multiple sclerosis (MS) is an inflammatory immune-mediated demyelinating disease that causes a challenging and disabling condition. Environmental and genetic factors play a role in appearing the state of the disease. Recent studies have shown that nuclear cofactor genes may play a role in the pathogenesis of MS. NCOA5 is a nuclear receptor coactivator independent of AF2 that modulates ERa-mediated transcription. This gene is involved in the pathogenesis of diseases such as psoriasis, Behcet's disease, and cancer. METHODS AND RESULTS: We investigated the relationship between the rs2903908 polymorphism of the NCOA5 gene and MS among 157 unrelated MS patients and 160 healthy controls by RT-PCR. The frequencies of the CC, CT, and TT genotypes were 19.87%, 37.82%, and 42.31%, respectively, for the MS group and 5.63%, 43.75%, and 50.62%, respectively, for the control group. The CC genotype and the C allele were found to be significantly higher in the patient group (the p values were 0.0002 and 0.003, respectively). CONCLUSIONS: The fact that the CC genotype was found to be significantly higher in the patient group compared to the control group (p = 0.0002) and that it had a statistically significantly higher OR value (OR, 95% CI = 4.16, 1.91-9.05) suggests that the C allele may recessively predispose to MS for this polymorphism. These results suggest for the first time that the NCOA5 gene may have an effect on the occurrence of MS through different molecular pathways, which are discussed in the manuscript.
Subject(s)
Multiple Sclerosis , Humans , Multiple Sclerosis/genetics , Genetic Predisposition to Disease , Gene Frequency/genetics , Polymorphism, Single Nucleotide/genetics , Genotype , Transcription Factors/genetics , Case-Control Studies , Nuclear Receptor Coactivators/geneticsABSTRACT
The plant powder "maras powder" (MP) has been used widely instead of cigarettes in the southeastern region of Turkey. The aim of this study was to assess the impacts of MP and cigarette smoking on the methylation and micronuclei (MN) formation in buccal cells of humans with a comparison to blood lymphocytes. DNA samples from 80 subjects (40 MP users, 20 tobacco smokers, 20 healthy volunteers) were analyzed for their genomic methylation status using Hpa II and Msp I digestions followed by a simple gel electrophoresis and ethidium bromide staining. A densitometric method was developed to measure the methylation in genomic DNA samples and the results were evaluated using a software program designed for this purpose. Buccal epithelial cells were collected from the same groups and examined for MN formation. The results indicated that a general genomic hypomethylation was present in almost all of the samples that were obtained from MP users and tobacco smokers. This hypomethylation was significant in MP users compared to smokers and healthy volunteers. The percentage of cells containing MN was 1.93 in MP users, 0.95 in healthy volunteers, and 1.82 in smokers. The MN frequency was significantly higher in MP users and smokers than in healthy volunteers. There was no statistical difference between smokers and MP users. Evidence indicates that MP usage induces DNA hypomethylation and increase frequency of MN formation.
Subject(s)
DNA Methylation/drug effects , Micronuclei, Chromosome-Defective/drug effects , Mouth Mucosa/cytology , Mouth Mucosa/drug effects , Nicotiana/chemistry , Tobacco, Smokeless/toxicity , Adult , Aged , Aged, 80 and over , DNA/chemistry , Epithelial Cells/drug effects , Humans , Middle Aged , Plants, Toxic , Powders , Smoking/adverse effectsABSTRACT
BACKGROUND: A plant powder called "Maras powder" is widely used instead of cigarette smoking in the South-Eastern region of Turkey. It has been confirmed that this powder comprises tobacco Nicotiana rustica L. METHODS: The aim of this study was to assess the effect of Maras powder and cigarette smoking on the P16 promotor hypermethylation. Twenty-two Maras powder users (Group I), 12 cigarette smokers (Group II), and 16 healthy controls who neither smoked nor used Maras powder (Group III) were included in the study. Hypermethylation of the P16 gene was examined using methylation-specific PCR (MSP) method in the blood of the three groups. RESULTS: Aberrant P16 methylation was found in 7 of the 22 (31.8%) in Group I, in 3 of 12 (25%) in Group II, and in 1 of 16 (6.25%) in Group III. CONCLUSION: Maras powder may be as harmful as cigarette smoking, leading to hypermethylation in P16 and warrants detailed studies on this subject.