scholarly journals Epigenetics of Friedreich’s Disease: Methylation of the (GAA)n-Repeats Region in FXN Gene

2019 ◽  
Vol 74 (2) ◽  
pp. 80-87
Author(s):  
Nataliya Yu. Abramycheva ◽  
Ekaterina Yu. Fedotova ◽  
Evgenii P. Nuzhnyi ◽  
Natalia S. Nikolaeva ◽  
Sergey A. Klyushnikov ◽  
...  
Keyword(s):  
Methylation Level ◽  
Direct Sequencing ◽  
Disease Onset ◽  
Inverse Correlation ◽  
Control Group ◽  
Cpg Sites ◽  
Intron 1 ◽  
Expanded Allele ◽  
Gaa Repeats ◽  
Gaa Expansion

Background: Friedreich’s disease (FD) is the most common hereditary ataxia. It is associated, most frequently, with homozygous GAA repeats expansion in intron 1 of the FXN gene. Methylation of the FXN gene can play an important role in the pathogenesis of FD. Aims: to study methylation pattern in CpG sites flanking GAA-expansion in intron 1 of the FXN gene in patients with FD and their heterozygous relatives as well as its relationship with clinical features. Materials and methods: We studied DNA samples from patients with FD (n=18), their relatives carrying heterozygous GAA expansion (n=12), and control group (n=15). Pattern of methylation was studied by direct sequencing of DNA regions after bisulphide processing. Results: We analyzed 18 CpG sites in the UP-GAA region of the gene (before GAA-repeats) and 12 CpG sites in the DOWN-GAA region (after GAA-repeats). In the UP-region, the mean methylation level of CpG sites in FD patients was higher compared to controls (n=15) (р0.05), while in the DOWN-region there was a decrease of mean methylation level in FD compared to controls (р0.05). Analysis of methylation level in different CpG sites in the UP-GAA region revealed hypermethylation for 15 of 18 CpG-sites as compared to controls (р0.05). The most significant differences in methylation level in the UP-GAA region were seen for CpG sites 50−54, 57 and 58. In contrast, in the DOWN-GAA region almost all CpG sites were fully methylated in the control group, while in FD patients methylation was significantly lower (р0.05). We revealed positive correlation of mean methylation level and more expanded allele length for the UP-GAA region in FD (r=0.63; p=0.03), and no correlations for the DOWN-GAA region. In heterozygous carriers we observed an analogous positive correlations in the UP-GAA region for CpG site 50 (r=0.77; p=0.04), while in the DOWN-GAA region there was inverse correlation of methylation with GAA repeat number in the expanded allele (r=-0.83, p=0.02). Negative correlation was found between the hypermethylation of some CpG-sites in the UP-GAA region and age of the disease onset (p0.05). Conclusion: We revealed hypermethylation in the UP-GAA region and hypomethylation in the DOWN-GAA region in patients with FD compared to controls and correlations of methylation level with the GAA expansion length and age of disease onset.

Genetic analysis of DNA methylation in dyslipidemia: a case-control study

2020 ◽  
Author(s):  
Yi-Tong Ma ◽  
Shuai Liu ◽  
Yang Li ◽  
Xian Wei ◽  
Dilare Adi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Methylation Level ◽  
Case Control Study ◽  
Case Control ◽  
Control Group ◽  
Cpg Sites ◽  
Heart Center ◽  
Medical University ◽  
The Relationship ◽  
Control Study

Abstract In our previous study, we explored the relationship between TBL2 gene DNA methylation and high-low-density lipoproteinemia (Hyper-LDL). However, Hyper-LDL is only one type of dyslipidemia. In order to expand the scope of clinical application, we explored the correlation between DNA methylation of genes related to lipid metabolism and dyslipidemia in this study. This study is a case-control study. A total of 180 samples were included in this study from the Heart Center of the First Affiliated Hospital of Xinjiang Medical University. The BSAS method was used to detect the DNA methylation levels and haplotypes of AMFR, FBXW7, INSIG1, INSIG2, MBTPS1 and GRINA genes. A total of 259 CpG sites and 14 regions were detected. The study found that a total of 24 CpG sites DNA methylation and 20 haplotypes were statistically different. The GRINA gene DNA methylation level in the dyslipidemia group was higher than that in the control group (2.68 vs 2.36, p = 0.04). ttttttttttttcttttttttttt is significant methylation haplotype of GRINA (p=0.017). Through logistics analysis, it is found that GRINA gene DNA methylation is an independent risk factor for dyslipidemia, and the increase of GRINA gene DNA methylation level will increase the prevalence of dyslipidemia.

scholarly journals GBA mutations p.N370S and p.L444P are associated with Parkinson's disease in patients from Northern Brazil

2019 ◽  
Vol 77 (2) ◽  
pp. 73-79 ◽  
Author(s):  
Carlos Eduardo de Melo Amaral ◽  
Patrick Farias Lopes ◽  
Juliana Cristina Cardoso Ferreira ◽  
Erik Artur Cortinhas Alves ◽  
Marcella Vieira Barroso Montenegro ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Direct Sequencing ◽  
Disease Onset ◽  
Control Group ◽  
Sample Number ◽  
Pcr Rflp ◽  
Pcr Products ◽  
Northern Brazil ◽  
Gba Gene

ABSTRACT Mutations of the GBA gene have been reported in patients with Parkinson's disease (PD) from a number of different countries, including Brazil. In order to confirm this pattern in a sample of PD patients from northern Brazil, we conducted a case-control study of the occurrence of the two most common mutations of the GBA gene (c.1226A>G; p.N370S and c.1448T>C; p.L444P) in a group of 81 PD patients and 81 control individuals, using PCR-RFLP, confirmed by the direct sequencing of the PCR products. In the patient group, three patients (3.7%) were heterozygous for the GBA c.1226A>G; p.N370S mutation, and three (3.7%) for GBA c.1448T>C; p.L444P Neither mutation was detected in the control group (p =0.0284). Patients with the c.1448T>C; p.L444P mutation showed a tendency to have an earlier disease onset, but a larger sample number is required to confirm this observation. Our results suggest an association between the GBA c.1226A>G; p.N370S and c.1448T>C; p.L444P mutations and the development of PD in the population of patients from the Northern Brazil.

scholarly journals Variable DNA methylation of aging-related genes is associated with male COPD

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Xizi Du ◽  
Lin Yuan ◽  
Mengping Wu ◽  
Meichao Men ◽  
Ruoxi He ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mrna Expression ◽  
Differentially Expressed Genes ◽  
Peripheral Blood ◽  
Methylation Level ◽  
Forced Expiratory Volume ◽  
Differentially Expressed ◽  
Control Group ◽  
Cpg Sites ◽  
Copd Patients

Abstract Background Chronic obstructive pulmonary disease (COPD) is a chronic lung inflammatory disease which has a close relationship with aging. Genome-wide analysis reveals that DNA methylation markers vary obviously with age. DNA methylation variations in peripheral blood have the potential to be biomarkers for COPD. However, the specific DNA methylation of aging-related genes in the peripheral blood of COPD patients remains largely unknown. Methods Firstly, 9 aging-related differentially expressed genes (DEGs) in COPD patients were screened out from the 25 aging-related genes profile through a comprehensive screening strategy. Secondly, qPCR and multiple targeted bisulfite enrichment sequencing (MethTarget) were used to detect the mRNA level and DNA methylation level of the 9 differentially expressed genes in the peripheral blood of 60 control subjects and 45 COPD patients. The candidate functional CpG sites were selected on the basis of the regulation ability of the target gene expression. Thirdly, the correlation was evaluated between the DNA methylation level of the key CpG sites and the clinical parameters of COPD patients, including forced expiratory volume in one second (FEV1), forced expiratory volume in one second as percentage of predicted volume (FEV1%), forced expiratory volume/ forced vital capacity (FEV/FVC), modified British medical research council (mMRC) score, acute exacerbation frequency and the situation of frequent of acute aggravation (CAT) score. Lastly, differentially methylated CpG sites unrelated to smoking were also determined in COPD patients. Results Of the 9 differentially expressed aging-related genes, the mRNA expression of 8 genes were detected to be significantly down-regulated in COPD group, compared with control group. Meanwhile, the methylated level of all aging-related genes was changed in COPD group containing 219 COPD-related CpG sites in total. Notably, 27 CpG sites of FOXO3 gene showed a lower False Discovery Rate (FDR) and higher methylation difference values. Also, some variable DNA methylation is associated with the severity of COPD. Additionally, of the 219 COPD-related CpG sites, 147 CpG sites were not related to smoking. Conclusion These results identified that the mRNA expression and DNA methylation level of aging-related genes were changed in male COPD patients, which provides a molecular link between aging and COPD. The identified CpG markers are associated with the severity of COPD and provide new insights into the prediction and identification of COPD.

scholarly journals Low-dose sublingual immunotherapy compared to subcutaneous immunotherapy and conventional therapy in childhood asthma

2016 ◽  
Vol 44 (6) ◽  
pp. 243
Author(s):  
Ariyanto Harsono
Keyword(s):  
Childhood Asthma ◽  
Low Dose ◽  
Sublingual Immunotherapy ◽  
Disease Onset ◽  
Ethics Committee ◽  
Subcutaneous Immunotherapy ◽  
Control Group ◽  
High Dose ◽  
Treat Ment ◽  
Group A

Background Evidence begin to accumulate that high-dose sub-lingual immunotherapy (SLIT) is as effective as subcutaneousimmunotherapy (SIT) in the treatment of childhood asthma.Since the capacity of sublingual area is similar whether the doseis high or low, the efficacy of low dose may be important to bestudied.Objective To investigate the efficacy of low-dose sublingual im-munotherapy in the treatment of childhood asthma.Methods Parents signed informed consent prior to enrollment,after having received information about the study. Patients weremoderate asthma aged 6-14 years with disease onset of lessthan 2 years before the commencement of the study and peakexpiratory flow rate (PEFR) variability of more than 15%. Pa-tients were randomly allocated into group A, B, and C whoreceived subcutaneous immunotherapy, low-dose sublingualimmunotherapy, and conventional asthma therapy, respectively.Randomization was stratified into two strata according to agei.e., 6-11 years or 11-14 years. Patients of each stratum wererandomized in block of three for each group. At the end of threemonths, lung function tests were repeated. The primary outcomewas PEFR variability at the end of the study. The study wasapproved by the Ethics Committee of Soetomo HospitalSurabaya.Results Distribution of variants as represented by sex, age,eosinophil count, and total IgE concentration were normal inthe three groups. PEFR variability decreased significantly from16.97+0.81 to 8.50+5.08 and 17.0+0.87 to 8.40+4.72 in groupreceiving SIT and SLIT, respectively (p<0.05), but decreasednot significantly from 17.00+0.83 to 10.82+0.5.41 in control group(p>0.05).Conclusion Low-dose SLIT is as efficacious as SIT in the treat-ment of moderate asthma in children

scholarly journals Expression of Transcript Variants of PTGS1 and PTGS2 Genes among Patients with Chronic Rhinosinusitis with Nasal Polyps

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 135
Author(s):  
Wioletta Pietruszewska ◽  
Wojciech Fendler ◽  
Marta Podwysocka ◽  
Adam J. Białas ◽  
Piotr Kuna ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Direct Sequencing ◽  
Adult Patients ◽  
Control Group ◽  
Reliable Test ◽  
Aggressive Disease ◽  
Transcript Variants

To date, there has been no reliable test to identify unfavorable course of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), especially in aspirin intolerant patients. The research aimed to analyze the expression of transcript variants of PTGS1 and PTGS2 genes in the pathobiology of the disease. The study was performed on 409 adult patients: 206 CRSwNP patients including 44 (21.36%) aspirin intolerant patients and 203 healthy volunteers in the control group. Transcript variants of the PTGS1 and PTGS2 genes named as follows: COX1.1 for NM_000962, COX1.2 for NM_080591, COX1.3 for NM_001271165.1, COX1.4 for NM_001271368.1, COX1.5 for NM_001271166.1, COX2.1 for NM_000963.3, COX2.2 for AY_151286 and COX2.3 for BQ_722004 were confirmed using direct sequencing and quantified using targeted qPCR. The coexistence of all examined transcript variants in the study and the control group and significant differences between both were found. In aspirin sensitive patients, the levels of COX1.2, COX1.3, COX1.4 and COX1.5 isoforms were higher compared to aspirin-tolerant patients. The severity of symptoms was bigger in patients with higher expressions of variants: COX1.1 (R with dCt = −0.134; p = 0.0490), COX1.3 (R = −0.1429; p = 0.0400) and COX1.5 (Rs = −0.1499; p = 0.032). The expression of COX1.1 (Rs = −0.098; p = 0.049) and COX1.5 (Rs = −0.141; p = 0.043) isoforms increased with polyposis advancement in endoscopy. With the CT extent of sinuses opacification, COX1.1 isoform also significantly increased (Rs = −0.163; p = 0.020). The isoforms COX1.3, COX1.4, COX1.5 and COX2.1 may promote milder CRSwNP course. On the contrary, the variants COX1.1, COX1.2 and COX2.2 may be involved in a more aggressive disease.

ELFIN, the United Kingdom preterm lactoferrin trial: interpretation and future questions

2020 ◽  
Author(s):  
Janet Elizabeth Berrington ◽  
William McGuire ◽  
NIcholas David Embleton
Keyword(s):  
United Kingdom ◽  
Preterm Infants ◽  
Late Onset ◽  
Disease Onset ◽  
Intervention Group ◽  
Control Group ◽  
Bovine Lactoferrin ◽  
The United Kingdom ◽  
Late Onset Sepsis ◽  
The Uk

Previous studies suggested that supplemental bovine lactoferrin (BLF) given to preterm infants (<32 weeks gestation) may reduce late onset sepsis (LOS) and necrotising enterocolitis (NEC), but have been underpowered. The Enteral Lactoferrin in Neonates (ELFIN) study, performed in the United Kingdom (UK), aimed to further address this issue with a well powered double blinded placebo controlled trial of >2200 preterm infants. ELFIN did not demonstrate a reduction in LOS or NEC, or several other clinically important measures. 316 (29%) of 1093 infants in the intervention group developed late-onset sepsis versus 334 (31%) of 1089 in the control group with an adjusted risk ratio of 0·95 (95% CI 0·86–1·04; p=0· 233). Reasons for the differences in ELFIN trial results and other studies may include population differences, the routine use of antifungals in the UK, timing of administration of the lactoferrin in relation to disease onset, or specific properties of the lactoferrin used in different trials. Further exploration is being undertaken in the UK NIHR funded Mechanisms Affecting the Guts of Preterm Infants in Enteral feeding trials (MAGPIE) study, for which results should be available soon.

scholarly journals Radiographic changes in TMJ in relation to serology and disease activity in RA patients

2020 ◽  
Vol 49 (1) ◽  
pp. 20190186
Author(s):  
Mostafa Mahmoud Youssef Mohamed ◽  
Mushira M. Dahaba ◽  
Mary Medhat Farid ◽  
Adel Mahmoud Ali Elsayed
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Joint Damage ◽  
Inverse Correlation ◽  
Rheumatoid Arthritis Group ◽  
Control Group ◽  
Significant Inverse Correlation ◽  
Moderate Disease ◽  
Condylar Head ◽  
Radiographic Changes

Objectives: This study was undertaken as an attempt to assess radiographic temporomandibular joint (TMJ) changes in relation to rheumatoid factor (RF), anticitrullinated protein (ACCP) antibodies and disease activity score 28 (DAS28) in rheumatoid arthritis (RA) patients to find the best predictor of rheumatoid affection of the TMJ with the ultimate goal of maintaining TMJ function and preventing joint damage. Methods: 20 Rheumatoid Arthritis patients as well as 20 volunteers were included in this study. RA group were assessed for RF, ACCP, DAS28. Both groups were assessed by CBCT for TMJ dimensions and radiographic osteoarthritic changes. All data were statistically analyzed. Results: Rheumatoid Arthritis group showed significantly less condylar height and more radiographic osteoarthritic changes than the control group. RF showed no significant correlation with either TMJ measurements or TMJ radiographic osteoarthritic changes. ACCP showed significant inverse correlation with condylar height and anteroposterior (AP) dimensions, but non-significant relation with mediolateral dimension and radiographic osteoarthritic changes. DAS28 showed significant inverse correlation with condylar AP and mediolateral dimensions. It also showed significant correlation with flattening of the TMJ condylar head and flattening of the articular fossa. Patients with high and moderate disease activity showed significantly smaller AP TMJ dimension than patients with low disease activity. Disease activity showed statistically significant direct correlation with all osteoarthritic changes except for erosions of the glenoid fossa and condyle. Conclusion: Disease Activity Score28 score and disease activity are strong indicators of TMJ affection in RA patients when compared to RF and ACCP. ACCP is a better indicator of changes in condylar measurements than TMJ osteoarthritic changes. While RF is the least efficient indicator of TMJ involvement in RA patients.

scholarly journals Expression of NMDA receptor and microRNA-219 in rats submitted to cerebral ischemia associated with alcoholism

2017 ◽  
Vol 75 (1) ◽  
pp. 30-35 ◽  
Author(s):  
Cristiane Iozzi Silva ◽  
Paulo Cézar Novais ◽  
Andressa Romualdo Rodrigues ◽  
Camila A.M. Carvalho ◽  
Benedicto Oscar Colli ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cerebral Ischemia ◽  
Brain Tissue ◽  
Wistar Rats ◽  
Molecular Mechanisms ◽  
Inverse Correlation ◽  
Control Group ◽  
The Brain ◽  
Lower Expression ◽  
Control Sham

ABSTRACT Alcohol consumption aggravates injuries caused by ischemia. Many molecular mechanisms are involved in the pathophysiology of cerebral ischemia, including neurotransmitter expression, which is regulated by microRNAs. Objective: To evaluate the microRNA-219 and NMDA expression in brain tissue and blood of animals subjected to cerebral ischemia associated with alcoholism. Methods: Fifty Wistar rats were divided into groups: control, sham, ischemic, alcoholic, and ischemic plus alcoholic. The expression of microRNA-219 and NMDA were analyzed by real-time PCR. Results: When compared to the control group, the microRNA-219 in brain tissue was less expressed in the ischemic, alcoholic, and ischemic plus alcoholic groups. In the blood, this microRNA had lower expression in alcoholic and ischemic plus alcoholic groups. In the brain tissue the NMDA gene expression was greater in the ischemic, alcoholic, and ischemic plus alcoholic groups. Conclusion: A possible modulation of NMDA by microRNA-219 was observed with an inverse correlation between them.

scholarly journals Fragile X Mental Retardation 1 (FMR1) Intron 1 Methylation in Blood Predicts Verbal Cognitive Impairment in Female Carriers of Expanded FMR1 Alleles: Evidence from a Pilot Study

2012 ◽  
Vol 58 (3) ◽  
pp. 590-598 ◽  
Author(s):  
David E Godler ◽  
Howard R Slater ◽  
Quang M Bui ◽  
Elsdon Storey ◽  
Michele Y Ono ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Cognitive Impairment ◽  
Fragile X ◽  
Cognitive Status ◽  
Verbal Iq ◽  
Fragile X Mental Retardation ◽  
Cpg Sites ◽  
Cgg Repeats ◽  
Intron 1 ◽  
Study Participants

Abstract BACKGROUND Cognitive status in females with mutations in the FMR1 (fragile X mental retardation 1) gene is highly variable. A biomarker would be of value for predicting which individuals were liable to develop cognitive impairment and could benefit from early intervention. A detailed analysis of CpG sites bridging exon 1 and intron 1 of FMR1, known as fragile X–related epigenetic element 2 (FREE2), suggests that a simple blood test could identify these individuals. METHODS Study participants included 74 control females (&lt;40 CGG repeats), 62 premutation (PM) females (55–200 CGG repeats), and 18 full-mutation (FM) females assessed with Wechsler intelligence quotient (IQ) tests. We used MALDI-TOF mass spectrometry to determine the methylation status of FREE2 CpG sites that best identified low-functioning (IQ &lt;70) FM females (&gt;200 CGG repeats), compared the results with those for Southern blot FMR1 activation ratios, and related these assessments to the level of production of the FMR1 protein product in blood. RESULTS A methylation analysis of intron 1 CpG sites 10–12 showed the highest diagnostic sensitivity (100%) and specificity (98%) of all the molecular measures tested for detecting females with a standardized verbal IQ of &lt;70 among the study participants. In the group consisting of only FM females, methylation of these sites was significantly correlated with full-scale IQ, verbal IQ, and performance IQ. Several verbal subtest scores showed strong correlation with the methylation of these sites (P = 1.2 × 10−5) after adjustment for multiple measures. CONCLUSIONS The data suggest that hypermethylation of the FMR1 intron 1 sites in blood is predictive of cognitive impairment in FM females, with implications for improved fragile X syndrome diagnostics in young children and screening of the newborn population.

Influence of Moderate, Daily Physical Activity On Body Composition and Blood Lipid Profile in Swedish Adults

2012 ◽  
Vol 9 (6) ◽  
pp. 867-874 ◽  
Author(s):  
Peter Pagels ◽  
Anders Raustorp ◽  
Trevor Archer ◽  
Ulf Lidman ◽  
Marie Alricsson
Keyword(s):  
Physical Activity ◽  
Energy Expenditure ◽  
Lipid Profile ◽  
Inverse Correlation ◽  
Blood Lipid ◽  
Daily Physical Activity ◽  
Moderate Intensity ◽  
Control Group ◽  
Brisk Walking ◽  
Blood Lipid Profile

Background:Health organizations suggest that adults ought to engage in at least 30 minutes of moderate-intensity daily physical activity. This study investigated the effects of a 30-minute single daily bout of brisk walking upon risk factors for coronary heart disease with blood lipid profile in particular.Methods:Thirty-three (25–45 y) adults, were randomly assigned into an exercise group (EG; n = 16, 9w) and a control group (CG; n = 17, 6w). The EG walked briskly 30 minutes daily during the 3-week test period. Compliance/adherence was maximal throughout the 3-week intervention due to stringent daily monitoring.Results:The EG showed a significant decrease in concentrations of low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) during the intervention period. A significant inverse correlation between Δ energy expenditure/day and Δ LDL-C (r = –0.39, P < .05) and an improvement in weight and BMI in the EG was found. Average steps during 30 minutes brisk walking bout was 3669 steps/bout generating a mean energy expenditure of 191 kcal/ bout.Conclusions:The most unique findings were that daily single bouts of moderate-intensity physical activity for 30 minutes, during 3 weeks, induced favorable effects upon body weight, BMI, and blood concentration of LDL-C and TC in healthy adults.

Sign in / Sign up

Export Citation Format

Share Document