scholarly journals Genetic Predictors of the Development and Recurrence of Graves' Disease

2018 ◽  
pp. S431-S439 ◽  
Author(s):  
D. VEJRAZKOVA ◽  
J. VCELAK ◽  
E. VACLAVIKOVA ◽  
M. VANKOVA ◽  
K. ZAJICKOVA ◽  
...  
Keyword(s):  
Genetic Factors ◽  
Current Knowledge ◽  
Twin Studies ◽  
Human Leukocyte ◽  
Graves Disease ◽  
Radioiodine Treatment ◽  
Leukocyte Antigen ◽  
Genetic Components ◽  
Genetic Predictors ◽  
First Choice

Graves' disease affects approximately 3 % of women and 0.5 % of men. The first-choice therapy is based on the administration of thyrostatic drugs. However, approximately half of patients relapse within two years of discontinuation. These patients must then decide whether to re-initiate thyrostatics, which may have serious side effects, or to undergo surgery or radioiodine treatment. Familial forms of Graves' disease indicate a significant genetic component, with twin studies demonstrating a contribution of genetic factors up to 70-80 %. The autoimmune nature of the disease involves the human leukocyte antigen (HLA) complex, which has a decisive impact on each individual's immune response. Within HLA, some variants of the DRB1, DQA1 and DQB1 genes appear to be possible predictors of the development and recurrence of Graves' disease. Outside the HLA region, many variants of immunocompetent genes have also been identified as potential Graves' disease predictors. Apart from the immune system, some thyroid-specific genes have been described in relation to the disease. Here, we present current knowledge regarding the genetic components involved in the development and recurrence of Graves' disease. Further, we present original pilot results from a cohort of Czech Graves' disease patients regarding the HLA variants.

scholarly journals Regression Mapping of Association between the Human Leukocyte Antigen Region and Graves Disease

2005 ◽  
Vol 76 (1) ◽  
pp. 157-163 ◽  
Author(s):  
Matthew J. Simmonds ◽  
Joanna M.M. Howson ◽  
Joanne M. Heward ◽  
Heather J. Cordell ◽  
Helen Foxall ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Graves Disease ◽  
Leukocyte Antigen ◽  
Human Leukocyte Antigen Region ◽  
Regression Mapping

scholarly journals Binding of Human Thyrotropin Receptor Peptides to a Graves’ Disease-Predisposing Human Leukocyte Antigen Class II Molecule

2000 ◽  
Vol 85 (3) ◽  
pp. 1176-1179 ◽  
Author(s):  
Yoshikuni Sawai ◽  
Leslie J. DeGroot
Keyword(s):  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Class Ii ◽  
Hla Class Ii ◽  
Graves Disease ◽  
T Cell Repertoire ◽  
Thyrotropin Receptor ◽  
Cell Repertoire ◽  
Peptide Epitopes ◽  
Leukocyte Antigen

Abstract Abstract There are many reports that Graves’ disease (GD) is associated with certain human leukocyte antigen (HLA) molecules, in particular DR3. Here we examined the characteristics of binding of human TSH receptor (TSHR) peptides to this disease-associated HLA class II molecule. DR3 molecules bind TSHR immuonodominant peptide epitopes with intermediate affinity. On the contrary, DR3 binds nonimmunogenic peptides either with poor affinity or not at all, with one exceptional peptide that has extremely high affinity. These results suggest that susceptibility to GD associated with inheritance of a specific HLA class II gene is due to the influence of the HLA molecule-TSHR peptide complex on the T cell repertoire.

scholarly journals The Human Leukocyte Antigen HLA DRB3∗0202/DQA1∗0501 Haplotype Is Associated with Graves’ Disease in African Americans

2000 ◽  
Vol 85 (4) ◽  
pp. 1545-1549 ◽  
Author(s):  
Qiao-Yi Chen ◽  
David Nadell ◽  
Xian-Yang Zhang ◽  
Anjli Kukreja ◽  
Yao-Jin Huang ◽  
...  
Keyword(s):  
African Americans ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Graves Disease ◽  
Leukocyte Antigen

scholarly journals Roles of Genes in the Susceptibility to and Severity of Rheumatoid Arthritis - A Review

1970 ◽  
Vol 13 (1) ◽  
pp. 51-54
Author(s):  
Abul Khair Ahmedullah ◽  
Shamim Ahmed ◽  
MD Ariful Islam
Keyword(s):  
Rheumatoid Arthritis ◽  
Genetic Factors ◽  
Human Leukocyte ◽  
Drug Efficacy ◽  
Autoimmune Disorder ◽  
Individual Variability ◽  
Unknown Etiology ◽  
Entire Genome ◽  
Gene Effects ◽  
Leukocyte Antigen

Rheumatoid arthritis (RA) is a chronic heterogeneous autoimmune disorder of unknown etiology. Genetic factors play an important role in susceptibility to RA as the heritability of RA is between 50% and 60%, with the human leukocyte antigen (HLA) locus accounting for at least 30% of overall genetic risk. It is conceivable that there is more than one susceptible gene(s) operative in RA, and an interaction of the relevant genes may predispose the offspring to develop the disease under certain conditions .Outside the major histocompatibility complex (MHC) region, some additional risk loci have been identified and validated including PTPN22, STAT4, PADI4, CTLA4 and others Genetic factors are also important in RA pharmacotherapy due to the gene-dependent activity of enzymes involved in the pharmacokinetics and/or pharmacodynamics of RA medications. Indeed, there is great variability in drug efficacy as well as adverse events associated with any anti-rheumatic therapy and genetics is thought to contribute significantly to this inter-individual variability in response. The ability to screen the entire genome for association to complex diseases has great potential for identifying gene effects. DOI: http://dx.doi.org/10.3329/jom.v13i1.10048 JOM 2012; 13(1): 51-54

scholarly journals The unusual association of Graves' disease, chronic spontaneous urticaria, and premature ovarian failure: report of a case and HLA haplotype characterization

2013 ◽  
Vol 57 (9) ◽  
pp. 748-752 ◽  
Author(s):  
Rosaria Maddalena Ruggeri ◽  
Giuseppe Vita ◽  
Anna Grazia D'Angelo ◽  
Paolina Quattrocchi ◽  
Rosaria Certo ◽  
...  
Keyword(s):  
Premature Ovarian Failure ◽  
Genetic Background ◽  
Marked Improvement ◽  
Human Leukocyte ◽  
Ovarian Failure ◽  
Chronic Spontaneous Urticaria ◽  
Graves Disease ◽  
Leukocyte Antigen ◽  
Unusual Association ◽  
Symptoms And Signs

Chronic spontaneous urticaria (CSU), defined as the occurrence of spontaneous wheals for more than six weeks, has been associated with autoimmune diseases. Herein, we report the unusual association of CSU, Graves' disease, and premature ovarian failure. Human leukocyte antigen (HLA) studies were performed. A 36-year-old woman presented symptoms and signs of hyperthyroidism for three months. In the same period, the patient complained of widespread urticarial wheals, intensely itchy, and poorly responsive to therapy with antihistaminic agents. Hyperthyroidism was confirmed biochemically, and treatment with methimazole was started. As hyperthyroidism improved, a marked improvement in her urticaria was also observed. However, the patient continued to complain of amenorrhea. Endocrine evaluation, at the age 38, was consistent with premature ovarian failure. This is the first report of coexistence of GD, CSU, and POF. The genetic background of such unusual association is a specific combination of HLA.

scholarly journals Multiple sclerosis and human leukocyte antigen genotypes: Focus on the Middle East and North Africa region

2020 ◽  
Vol 6 (1) ◽  
pp. 205521731988177
Author(s):  
Zhila Maghbooli ◽  
Mohammad Ali Sahraian ◽  
Abdorreza Naser Moghadasi
Keyword(s):  
Multiple Sclerosis ◽  
Middle East ◽  
Human Leukocyte Antigen ◽  
North Africa ◽  
Human Leukocyte ◽  
Genetic Studies ◽  
Leukocyte Antigen ◽  
Genetic Components ◽  
Control Designs

Recent reports have demonstrated that the prevalence of multiple sclerosis (MS) is increasing in the Middle East and North Africa region. There is also emerging evidence regarding the genetic components of MS risk. This review provides an overview of the role of genetic factors in MS susceptibility by examining human leukocyte antigen loci in patients within the Middle East and North Africa region. Most of the genetic studies conducted in the Middle East and North Africa region have been based on case–control designs, which cannot confirm direct causality of genetic variants on MS susceptibility. Moreover, there are very limited and inconsistent studies on human leukocyte antigen class I and II (DQA and DQB) in MS patients of the Middle East and North Africa region. To identify common risk haplotypes in the Middle East and North Africa region or its sub-populations, further longitudinal studies will be required.

scholarly journals An Intronic HCP5 Variant Is Associated With Age of Onset and Susceptibility to Graves Disease in UK and Polish Cohorts

2020 ◽  
Vol 105 (9) ◽  
pp. e3277-e3284 ◽  
Author(s):  
Laura Claire Lane ◽  
Aleksander Kuś ◽  
Tomasz Bednarczuk ◽  
Artur Bossowski ◽  
Jacek Daroszewski ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Meta Analysis ◽  
Human Leukocyte ◽  
Graves Disease ◽  
Ribonucleic Acids ◽  
Young Onset ◽  
Leukocyte Antigen ◽  
Genotype Frequencies ◽  
The Uk

Abstract Context The genetic background of young-onset Graves disease (GD) remains largely unknown. An intronic variant in human leukocyte antigen (HLA) complex P5 (HCP5) has previously been associated with GD susceptibility and age of onset in a cohort of Polish patients. Objective We aimed to investigate the association of the HCP5 variant rs3094228 with GD susceptibility and age of onset in a UK cohort and conduct a meta-analysis of UK and Polish data. Design and Participants rs3094228 was genotyped in 469 UK patients with GD using Taqman chemistry. Genotype frequencies were compared with genotypic data available from the Wellcome Trust case-control consortium using logistic regression analysis. To determine whether rs3094228 is independently associated with age of GD onset, the HLA DRB1*0301 tagging variant, rs535777, was also genotyped. Results The C allele of rs3094228 was overrepresented in the UK GD cohort compared with controls (P allele=5.08 × 10–9, odds ratio 1.76; [95% confidence interval, 1.46-2.13]). This association was more marked in young-onset GD (<30 years) (P allele=1.70 × 10–10 vs P allele=0.0008). The meta-analysis of UK and Polish data supported the association of the C allele with GD susceptibility (P allele=1.79 × 10–5) and age of onset (P allele=5.63 × 10–8). Haplotype analysis demonstrated that rs3094228 is associated with age of GD onset (P = 2.39 × 10-6) independent of linkage disequilibrium with HLA DRB1*0301. Conclusion The rs3094228 HCP5 polymorphism is independently associated with GD susceptibility and age of onset in a UK GD cohort. Our findings indicate a potential role of long noncoding ribonucleic acids, including HCP5, in GD pathogenesis, particularly in the younger population.

scholarly journals The ubiquitin-like modifier FAT10 – much more than a proteasome-targeting signal

2020 ◽  
Vol 133 (14) ◽  
pp. jcs246041
Author(s):  
Annette Aichem ◽  
Marcus Groettrup
Keyword(s):  
Current Knowledge ◽  
Human Leukocyte ◽  
Cell Types ◽  
26S Proteasome ◽  
Covalent Interaction ◽  
Leukocyte Antigen ◽  
Differential Outcomes ◽  
Interaction Partners ◽  
Targeting Signal ◽  
Necrosis Factor

ABSTRACTHuman leukocyte antigen (HLA)-F adjacent transcript 10 (FAT10) also called ubiquitin D (UBD) is a member of the ubiquitin-like modifier (ULM) family. The FAT10 gene is localized in the MHC class I locus and FAT10 protein expression is mainly restricted to cells and organs of the immune system. In all other cell types and tissues, FAT10 expression is highly inducible by the pro-inflammatory cytokines interferon (IFN)-γ and tumor necrosis factor (TNF). Besides ubiquitin, FAT10 is the only ULM which directly targets its substrates for degradation by the 26S proteasome. This poses the question as to why two ULMs sharing the proteasome-targeting function have evolved and how they differ from each other. This Review summarizes the current knowledge of the special structure of FAT10 and highlights its differences from ubiquitin. We discuss how these differences might result in differential outcomes concerning proteasomal degradation mechanisms and non-covalent target interactions. Moreover, recent insights about the structural and functional impact of FAT10 interacting with specific non-covalent interaction partners are reviewed.

scholarly journals A One-Tube Polymerase Chain Reaction Protocol Demonstrates CC Chemokine Overexpression in Graves’ Disease Glands

1999 ◽  
Vol 84 (8) ◽  
pp. 2873-2882
Author(s):  
Yaqoub Ashhab ◽  
Orlando Dominguez ◽  
Mireia Sospedra ◽  
Carme Roura-Mir ◽  
Anna Lucas-Martín ◽  
...  
Keyword(s):  
Human Leukocyte ◽  
Needle Aspiration ◽  
Graves Disease ◽  
Tissue Samples ◽  
Autoimmune Thyroid ◽  
Leukocyte Antigen ◽  
Cc Chemokine ◽  
Inflammatory Protein ◽  
Cc Chemokines ◽  
Polymerase Chain

An adaptation of mixed oligonucleotide primed amplification of complementary DNA to detect the profile of CC chemokines in biological samples is presented. By introducing normalization, two correction coefficients, performing a single amplification reaction, and five parallel hybridizations, intrasample and intersample comparisons can be reliably made. This protocol of single tube PCR CC chemokine profiling was applied to tissue samples from an autoimmune thyroid condition, Graves’ disease, and from a nonautoimmune condition, multinodular goiter. Results demonstrate overexpression of CC chemokines in Graves’ disease, statistically significant for macrophage inflammatory protein-1α and -1β, which correlated with the aberrant human leukocyte antigen class II expression by thyrocytes, as assessed by flow cytometry. Overexpression of CC chemokines probably plays a major role in determining the characteristics of the lymphocytes migrating to the thyroid gland and influences the course of the disease. The study of chemokine profile should be more informative than the study of isolated chemokines and cytokines, and as it can be applied to fine needle aspiration biopsies, it may be useful to clinical research.

Sign in / Sign up

Export Citation Format

Share Document