scholarly journals The immunogenetics of multiple sclerosis. The frequency of HLA-alleles class 1 and 2 is lower in Southern Brazil than in the European population

2016 ◽  
Vol 74 (8) ◽  
pp. 607-616 ◽  
Author(s):  
Lineu Cesar Werneck ◽  
Paulo José Lorenzoni ◽  
Raquel Cristina Arndt ◽  
Cláudia Suemi Kamoi Kay ◽  
Rosana Herminia Scola
Keyword(s):  
Multiple Sclerosis ◽  
High Resolution ◽  
Direct Sequencing ◽  
Positive Association ◽  
Statistical Correlation ◽  
European Population ◽  
Southern Brazil ◽  
Bonferroni Correction ◽  
Hla Alleles ◽  
Class 1

ABSTRACT Objective To study the HLA of class 1and 2 in a multiple sclerosis (MS) population to verify the susceptibility for the disease in the Southern Brazil. Methods We analyzed patients with MS and controls, by direct sequencing of the genes related to HLA DRB1, DQB1, DPB1, A, B and C alleles with high resolution techniques. Results We found a lower frequency of all HLA alleles class 1 and 2 in MS and controls comparing to the European population. Several alleles had statistical correlation, but after Bonferroni correction, the only allele with significance was the HLA-DQB1*02:03, which has a positive association with MS. Conclusions Our data have different frequency of HLA-alleles than the previous published papers in the Southeast Brazil and European population, possible due to several ethnic backgrounds.

scholarly journals Parental mosaicism in Marfan and Ehlers–Danlos syndromes and related disorders

2021 ◽  
Author(s):  
Bertrand Chesneau ◽  
Aurélie Plancke ◽  
Guillaume Rolland ◽  
Nicolas Chassaing ◽  
Christine Coubes ◽  
...  
Keyword(s):  
High Resolution ◽  
Marfan Syndrome ◽  
High Resolution Melting ◽  
De Novo ◽  
Direct Sequencing ◽  
Causal Variant ◽  
Connective Tissue Disorder ◽  
High Resolution Melting Analysis ◽  
Aortic Diseases ◽  
Melting Analysis

AbstractMarfan syndrome (MFS) is a heritable connective tissue disorder (HCTD) caused by pathogenic variants in FBN1 that frequently occur de novo. Although individuals with somatogonadal mosaicisms have been reported with respect to MFS and other HCTD, the overall frequency of parental mosaicism in this pathology is unknown. In an attempt to estimate this frequency, we reviewed all the 333 patients with a disease-causing variant in FBN1. We then used direct sequencing, combined with High Resolution Melting Analysis, to detect mosaicism in their parents, complemented by NGS when a mosaicism was objectivized. We found that (1) the number of apparently de novo events is much higher than the classically admitted number (around 50% of patients and not 25% as expected for FBN1) and (2) around 5% of the FBN1 disease-causing variants were not actually de novo as anticipated, but inherited in a context of somatogonadal mosaicisms revealed in parents from three families. High Resolution Melting Analysis and NGS were more efficient at detecting and evaluating the level of mosaicism compared to direct Sanger sequencing. We also investigated individuals with a causal variant in another gene identified through our “aortic diseases genes” NGS panel and report, for the first time, on an individual with a somatogonadal mosaicism in COL5A1. Our study shows that parental mosaicism is not that rare in Marfan syndrome and should be investigated with appropriate methods given its implications in patient’s management.

scholarly journals Adherence to Therapy, Physical and Mental Quality of Life in Patients with Multiple Sclerosis

2021 ◽  
Vol 11 (7) ◽  
pp. 672
Author(s):  
Alessandra Buja ◽  
Guendalina Graffigna ◽  
Simona F. Mafrici ◽  
Tatjana Baldovin ◽  
Carlo Pinato ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Sclerosis ◽  
Behavioral Interventions ◽  
Positive Association ◽  
Cross Sectional Study ◽  
Health Index ◽  
Online Questionnaire ◽  
Cross Sectional ◽  
Adherence To Therapy

Ensuring multiple sclerosis (MS) patients’ adherence to therapy is often challenging, but it is crucial to their survival and health-related quality of life (HRQoL). The aim of the present study was to outline connections between adherence, physical and mental HRQoL, levels of psychological readiness to engage in a treatment, levels of social support, anthropometric, socio-demographic and clinical factors in patients suffering from MS. This cross-sectional study involved a sample of 237 Italian MS patients. A survey was conducted with a structured self-administered online questionnaire using validated measures of quality of life, adherence to therapy and anthropometric, socio-demographic, psychological and clinical variables. A path analysis was used to test the overall structure of the associations between the variables. The pathway indicates a positive association between mental health index and a stronger degree of engagement and being or having been in a long-term relationship. Physical health index was positively associated with age, having an occupation, and having a specific form of MS. Having had relapses in the previous year raised the odds of better adherence to therapy, while an increase in Body Mass Index (BMI) reduced them. Our findings could help in the management of MS patients, promoting behavioral interventions that take the psychological and socio-demographic peculiarities of each patient into account with a view to improving their adherence to therapy.

scholarly journals Metabolic syndrome and endocrine disrupting chemicals: exposure and health effects

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
E Haverinen ◽  
R Lange ◽  
H Tolonen
Keyword(s):  
Metabolic Syndrome ◽  
Bisphenol A ◽  
Health Effects ◽  
Endocrine Disrupting Chemicals ◽  
Positive Association ◽  
Human Biomonitoring ◽  
European Population ◽  
Priority Substances ◽  
Metabolic Disturbances ◽  
Endocrine Disrupting

Abstract Increasing prevalence of metabolic syndrome (MetS) is causing significant health burden among the European population. Current knowledge supports the notion that endocrine disrupting chemicals (EDCs) interfere with human metabolism and hormonal balance, contributing to the conventionally recognized life-style related risk factors for MetS. In relation to the Human biomonitoring initiative (HBM4EU) five priority substances (Bisphenol A, Per- and polyfluoroalkyl substances (PFASs), Phthalates, Cadmium and Arsenic) and their association with adverse metabolic health effects were examined. A methodological framework for scoping reviews was followed to increase consistency and transparency throughout the process. A literature review was conducted to identify epidemiological studies focusing on the association between MetS or its individual components and the five HBM4EU priority substances. Human biomonitoring studies have been able to present evidence supporting EDC exposure and development of individual MetS components; however the strength of the association varies between the components and EDCs. Most of the identified literature examined Bisphenol A and Phthalate exposure, usually targeting obesity, anthropometrics or glucose metabolism. Evidence suggests a positive association between Bisphenol A and Phthalate exposure and obesity-related components. The substance group of PFASs indicated weakest association, as the results were inconsistent and were suggestive only for a positive association with development of dyslipidaemia. Current evidence on metabolic disturbances and EDCs are inconclusive and fragmented, hence establishing harmonized and standardized human biomonitoring procedures among the European population are needed. Rigorous and ongoing human biomonitoring in combination with health monitoring could provide comprehensive information on EDC exposure and association of metabolic disturbances. Key messages EDC exposure is ubiquitous within European population, hence more human biomonitoring in combination with health surveys is needed to strengthen knowledge on human’s metabolic health. MetS is an increasing global health concern, which requires novel approaches to tackle the challenge.

scholarly journals High Resolution Haplotype Analyses of Classical HLA Genes in Families With Multiple Sclerosis Highlights the Role of HLA-DP Alleles in Disease Susceptibility

2021 ◽  
Vol 12 ◽  
Author(s):  
Kazutoyo Osoegawa ◽  
Lisa E. Creary ◽  
Gonzalo Montero-Martín ◽  
Kalyan C. Mallempati ◽  
Sridevi Gangavarapu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Statistical Significance ◽  
Hla Class I ◽  
Protective Effects ◽  
Genetic Associations ◽  
Hla Alleles ◽  
Hla Genes ◽  
Haplotype Allele ◽  
Family Based ◽  
Hla Haplotypes

Multiple sclerosis (MS) susceptibility shows strong genetic associations with HLA alleles and haplotypes. We genotyped 11 HLA genes in 477 non-Hispanic European MS patients and their 954 unaffected parents using a validated next-generation sequencing (NGS) methodology. HLA haplotypes were assigned unequivocally by tracing HLA allele transmissions. We explored HLA haplotype/allele associations with MS using the genotypic transmission disequilibrium test (gTDT) and multiallelic TDT (mTDT). We also conducted a case-control (CC) study with all patients and 2029 healthy unrelated ethnically matched controls. We performed separate analyses of 54 extended multi-case families by reviewing transmission of haplotype blocks. The haplotype fragment including DRB5*01:01:01~DRB1*15:01:01:01 was significantly associated with predisposition (gTDT: p < 2.20e-16; mTDT: p =1.61e-07; CC: p < 2.22e-16) as reported previously. A second risk allele, DPB1*104:01 (gTDT: p = 3.69e-03; mTDT: p = 2.99e-03; CC: p = 1.00e-02), independent from the haplotype bearing DRB1*15:01 was newly identified. The allele DRB1*01:01:01 showed significant protection (gTDT: p = 8.68e-06; mTDT: p = 4.50e-03; CC: p = 1.96e-06). Two DQB1 alleles, DQB1*03:01 (gTDT: p = 2.86e-03; mTDT: p = 5.56e-02; CC: p = 4.08e-05) and DQB1*03:03 (gTDT: p = 1.17e-02; mTDT: p = 1.16e-02; CC: p = 1.21e-02), defined at two-field level also showed protective effects. The HLA class I block, A*02:01:01:01~C*03:04:01:01~B*40:01:02 (gTDT: p = 5.86e-03; mTDT: p = 3.65e-02; CC: p = 9.69e-03) and the alleles B*27:05 (gTDT: p = 6.28e-04; mTDT: p = 2.15e-03; CC: p = 1.47e-02) and B*38:01 (gTDT: p = 3.20e-03; mTDT: p = 6.14e-03; CC: p = 1.70e-02) showed moderately protective effects independently from each other and from the class II associated factors. By comparing statistical significance of 11 HLA loci and 19 haplotype segments with both untruncated and two-field allele names, we precisely mapped MS candidate alleles/haplotypes while eliminating false signals resulting from ‘hitchhiking’ alleles. We assessed genetic burden for the HLA allele/haplotype identified in this study. This family-based study including the highest-resolution of HLA alleles proved to be powerful and efficient for precise identification of HLA genotypes associated with both, susceptibility and protection to development of MS.

Positive association ofDRB1*04andDRB1*15alleles with Fyaimmunization in a Southern European population

Transfusion ◽  
2009 ◽  
Vol 49 (11) ◽  
pp. 2412-2417 ◽  
Author(s):  
Chistophe Picard ◽  
Coralie Frassati ◽  
Agnes Basire ◽  
Stephan Buhler ◽  
Vital Galicher ◽  
...  
Keyword(s):  
Positive Association ◽  
European Population

scholarly journals Multiple sclerosis and psychiatric disorders: Comorbidity and sibling risk in a nationwide Swedish cohort

2014 ◽  
Vol 20 (14) ◽  
pp. 1881-1891 ◽  
Author(s):  
Viktoria Johansson ◽  
Cecilia Lundholm ◽  
Jan Hillert ◽  
Thomas Masterman ◽  
Paul Lichtenstein ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Bipolar Disorder ◽  
Psychiatric Disorders ◽  
Psychiatric Patients ◽  
Familial Risk ◽  
Positive Association ◽  
Protective Mechanisms ◽  
Genetic Liability ◽  
Sibling Comparison ◽  
National Patient

Background: Psychiatric disorders are known to be prevalent in multiple sclerosis (MS). Objective: The objective of this paper is to study comorbidity between MS and bipolar disorder, schizophrenia and depression in a nationwide cohort and to determine whether shared genetic liability underlies the putative association. Methods: We identified ICD-diagnosed patients with MS ( n = 16,467), bipolar disorder ( n = 30,761), schizophrenia ( n = 22,781) and depression ( n = 172,479) in the Swedish National Patient Register and identified their siblings in the Multi-Generation Register. The risk of MS was compared in psychiatric patients and in matched unexposed individuals. Shared familial risk between MS and psychiatric disorders was estimated by sibling comparison. Results: The risk of MS was increased in patients with bipolar disorder (hazard ratio (HR) 1.8, 95% confidence interval (CI) 1.6–2.2, p < 0.0001) and depression (HR 1.9, 95% CI 1.7–2.0, p < 0.0001). MS risk in schizophrenia was decreased (HR 0.6, 95% CI 0.4–0.9, p = 0.005). The association between having a sibling with a psychiatric disorder and developing MS was not significant. Conclusion: We found a strong positive association between MS and bipolar disorder and depression that could not be explained by genetic liability. The unexpected negative association between MS and schizophrenia might be spurious or indicate possible protective mechanisms that warrant further exploration.

Two agarose electrophoretic systems for demonstration of oligoclonal bands in cerebrospinal fluid compared.

1980 ◽  
Vol 26 (2) ◽  
pp. 343-345 ◽  
Author(s):  
B Gerson ◽  
F J Krolikowski ◽  
I M Gerson
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
High Resolution ◽  
Thin Layer ◽  
Oligoclonal Bands ◽  
System Sensitivity ◽  
Electrophoretic Patterns ◽  
Clinical Laboratories ◽  
Two Systems

Abstract Demonstration of oligoclonal bands by electrophoresis of cerebrospinal fluid is an important aid in establishing the diagnosis of multiple sclerosis. Electrophoretic systems vary in their effectiveness in doing so. We compared two systems in this respect. For a thin-layer agarose system, sensitivity was less (47%) than for a high-resolution agarose system (87%). Each system had good specificity (92 and 85%, respectively). Interpretation of electrophoretic patterns for cerebrospinal fluid should be available in clinical laboratories. Further, the best available system should be used for demonstration of oligoclonal bands.

scholarly journals Evaluation of the Influence of Genetic Variants of SLC2A9 (GLUT9) and SLC22A12 (URAT1) on the Development of Hyperuricemia and Gout

2020 ◽  
Vol 9 (8) ◽  
pp. 2510
Author(s):  
Katerina Pavelcova ◽  
Jana Bohata ◽  
Marketa Pavlikova ◽  
Eliska Bubenikova ◽  
Karel Pavelka ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Uric Acid ◽  
Genetic Variants ◽  
Biochemical Parameters ◽  
Previous Analysis ◽  
Direct Sequencing ◽  
Low Frequency ◽  
European Population ◽  
The Body ◽  
Genes Encoding

Urate transporters, which are located in the kidneys, significantly affect the level of uric acid in the body. We looked at genetic variants of genes encoding the major reabsorption proteins GLUT9 (SLC2A9) and URAT1 (SLC22A12) and their association with hyperuricemia and gout. In a cohort of 250 individuals with primary hyperuricemia and gout, we used direct sequencing to examine the SLC22A12 and SLC2A9 genes. Identified variants were evaluated in relation to clinical data, biochemical parameters, metabolic syndrome criteria, and our previous analysis of the major secretory urate transporter ABCG2. We detected seven nonsynonymous variants of SLC2A9. There were no nonsynonymous variants of SLC22A12. Eleven variants of SLC2A9 and two variants of SLC22A12 were significantly more common in our cohort than in the European population (p = 0), while variants p.V282I and c.1002+78A>G had a low frequency in our cohort (p = 0). Since the association between variants and the level of uric acid was not demonstrated, the influence of variants on the development of hyperuricemia and gout should be evaluated with caution. However, consistent with the findings of other studies, our data suggest that p.V282I and c.1002+78A>G (SLC2A9) reduce the risk of gout, while p.N82N (SLC22A12) increases the risk.

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