Primary Sjögren Syndrome

2015 ◽  
Author(s):  
E. William St. Clair ◽  
Melissa A. Wells
Keyword(s):  
Keratoconjunctivitis Sicca ◽  
Association Studies ◽  
Connective Tissue Diseases ◽  
Lymphocyte Activation ◽  
Genome Wide Association Studies ◽  
Dry Eyes ◽  
Rheumatologic Diseases ◽  
Genome Wide ◽  
Chronic Inflammatory Condition

This review focuses on the primary category of Sjögren syndrome (SS), a chronic inflammatory condition that is defined by the presence of dry eyes (keratoconjunctivitis sicca) or dry mouth (xerostomia) in the absence of other rheumatologic diseases. SS may also have extraglandular manifestations in the form of pulmonary, renal, gastrointestinal, and neurologic diseases that can cause significant morbidity and increased mortality and is distinct from other connective tissue diseases. Although the etiology of primary SS is unknown, genome-wide association studies are continuing to reveal that susceptibility to the disease is based on genetic predisposition; patients with primary SS have been identified with several non–major histocompatibility complex genetic polymorphisms that are statistically associated with increased disease susceptibility. In a recent study, blood CD4+ T cells from patients with primary SS were shown to differ in their patterns of DNA methylation compared with healthy controls and demonstrated that many genes involved in lymphocyte activation and the immune response were poised for transcription. Treatment of primary SS mainly involves relief of symptoms and prevention of long-term disease complications. Although biologic therapies have been studied, the results so far have been either negative or inconclusive. This review contains 5 highly rendered figures, 5 tables, and 89 references.

Current Challenges in the Genetics of Psoriatic Arthritis: A Report from the GRAPPA 2009 Annual Meeting

2011 ◽  
Vol 38 (3) ◽  
pp. 564-566 ◽  
Author(s):  
PROTON RAHMAN
Keyword(s):  
Psoriatic Arthritis ◽  
Annual Meeting ◽  
Association Studies ◽  
Environment Interaction ◽  
Genome Wide Association Studies ◽  
Novel Genes ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Genome Wide

Psoriasis and psoriatic arthritis (PsA) are heterogeneous diseases. While both have a strong genetic basis, it is strongest for PsA, where fewer investigators are studying its genetics. Over the last year the number of independent genetic loci associated with psoriasis has substantially increased, mostly due to completion of multiple genome-wide association studies (GWAS) in psoriasis. At least 2 GWAS efforts are now under way in PsA to identify novel genes in this disease; a metaanalysis of genome-wide scans and further studies must follow to examine the genetics of disease expression, epistatic interaction, and gene-environment interaction. In the long term, it is anticipated that genome-wide sequencing is likely to generate another wave of novel genes in PsA. At the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) in Stockholm, Sweden, in 2009, members discussed issues and challenges regarding the advancement of the genetics of PsA; results of those discussions are summarized here.

scholarly journals Identification of potential key genetic factors in the long-term success of Shigella as pathogens

2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
Rebecca Bennett ◽  
Rebecca Bengtsson ◽  
Kate Baker
Keyword(s):  
Genetic Factors ◽  
Association Studies ◽  
Enteric Bacteria ◽  
Continuous Variable ◽  
Genome Wide Association Studies ◽  
Phenotypic Analysis ◽  
Global Management ◽  
Genome Wide ◽  
New Antibiotics

Bacterial of the genus Shigella are a major contributor to the global diarrhoea burden causing 100,000 deaths per annum globally. Further to this, increasing antibiotic resistance in Shigella and the lack of a licenced vaccine has led WHO to recognise Shigella as a priority organism for the development of new antibiotics. Understanding what drives the long-term persistence and success of this pathogen will thus aid the global management of shigellosis and may identify targets relevant to other enteric bacteria. To identify key genetic drivers of Shigella evolution over the past 100 years, we have used the historical Murray collection; comprising several hundred pre-antibiotic era (1917 – 1954) Enterobacteriaceae from diverse geographical locations. We employed genome-wide association studies to sequences from over 100 Shigella isolates from the Murray collection alongsidemore modern (i.e. 1950s – 2018) isolates to identify genetic factors (SNPs and genes) significantly associated with time as a continuous variable. GWAS hits (e.g. a putative resistance protein) then underwent variation, functional and phenotypic analysis to examine the plausibility of their role in shaping Shigella populations and as potential targets for managing this pathogen.

Pharmacogenetics studies in stroke patients treated with rtPA: a review of the most interesting findings

2021 ◽  
Author(s):  
Laia Llucià-Carol ◽  
Elena Muiño ◽  
Cristina Gallego-Fabrega ◽  
Jara Cárcel-Márquez ◽  
Jesus Martín-Campos ◽  
...  
Keyword(s):  
Association Studies ◽  
Recombinant Tissue Plasminogen Activator ◽  
Genome Wide Association Studies ◽  
Factors Associated ◽  
The Past ◽  
Genome Wide ◽  
Candidate Strategy ◽  
Tissue Plasminogen ◽  
Functional Deterioration

Recombinant tissue-plasminogen activator (rtPA) is the only drug used during the acute phase of stroke. Despite its important benefits, a percentage of patients suffer symptomatic hemorrhagic transformations or a lack of early recanalization rates. These undesirable effects are associated with acute neurological and long-term functional deterioration. For the past 20 years, pharmacogenetic studies have tried to find the genetic risk factors associated with rtPA response. Most of these studies have used a gene-candidate strategy; however, recent genome-wide association studies have emerged indicating that genetic predisposition could modulate rtPA response. This review summarizes the most interesting findings in this field, including which genes and genetic variations are associated with hemorrhagic transformations and recanalization rates after thrombolytic therapy.

scholarly journals Ultralow amounts of DNA from long-term archived serum samples produce quality genotypes

2019 ◽  
Vol 28 (4) ◽  
pp. 521-524
Author(s):  
Trine B. Rounge ◽  
Marianne Lauritzen ◽  
Sten Even Erlandsen ◽  
Hilde Langseth ◽  
Oddgeir Lingaas Holmen ◽  
...  
Keyword(s):  
Association Studies ◽  
Genome Wide Association Studies ◽  
Serum Samples ◽  
Dna Yield ◽  
Genome Wide ◽  
Thermo Fisher Scientific ◽  
Storage Effects ◽  
The Mean ◽  
And Storage

Abstract While genotyping studies are scavenging for suitable samples to analyze, large serum collections are currently left unused as they are assumed to provide insufficient amounts of DNA for array-based genotyping. Long-term stored serum is considered to be difficult to genotype since preanalytical treatments and storage effects on DNA yields are not well understood. Successful genotyping of such samples has the potential to activate large biobanks for future genome-wide association studies (GWAS). We aimed to evaluate genotyping of ultralow amounts of DNA from samples stored up to 45 years in the Janus Serum Bank with two commercially available platforms. 64 samples, with various preanalytical treatments, were genotyped on the Axiom Array from Thermo Fisher Scientific and a subset of 24 samples with slightly higher yield were genotyped on the HumanCoreExome array from Illumina. Our results showed that about 80% of the serum samples produced call rates with the Axiom arrays that would be satisfactory in GWAS. The mean DNA yield was 5.8 ng as measured with PicoGreen, 3–6% of recommended yield. The failed samples had on average lower input amounts of DNA. All serum samples genotyped on the HumanCoreExome with a standard and FFPE protocol produced GWAS satisfactory call rates, with mean 97.57% and 98.35% call rates, respectively. The mean yield was 10.65 ng, 6% of the recommendations. Successful array-based genotyping of ultralow DNA yields from serum samples stored up to 45 years is possible. These results demonstrate the potential to activate large serum biobank collections for future studies.

scholarly journals Pharmacologic treatment of restless legs syndrome

2020 ◽  
Vol 19 ◽  
Author(s):  
Qing Lv ◽  
Xinlin Wang ◽  
Tetsuya Asakawa ◽  
Xiao Ping Wang
Keyword(s):  
Restless Legs Syndrome ◽  
Association Studies ◽  
Cell Loss ◽  
Genome Wide Association Studies ◽  
Neural Pathways ◽  
Dopaminergic Drugs ◽  
Restless Legs ◽  
Genome Wide ◽  
Mechanistic Basis

: Restless legs syndrome (RLS)/Willis-Ekbom disease is a neurologic disorder characterized by a strong desire to move when at rest (usually in the evening) and paraesthesia in their lower legs. The most widely used therapies for first-line treatment of RLS are dopaminergic drugs; however, their long-term use can lead to augmentation. α2δ Ligands, opioids, iron, glutamatergic drugs, adenosine, and sleep aids have been investigated as alternatives. The pathogenesis of RLS is not well understood. Despite the efficacy of dopaminergic drugs in the treatment of this disorder, unlike in Parkinson’s disease dopaminergic cell loss in the substantia nigra has not been observed in RLS. The etiology of RLS is likely complex, involving multiple neural pathways. RLS-related genes identified in genome-wide association studies can provide insight into the mechanistic basis and pathophysiology of RLS. Here we review the current treatments and knowledge of the mechanisms underlying RLS.

scholarly journals Genetic history of Calabrian Greeks reveals ancient events and long term isolation in the Aspromonte area of Southern Italy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stefania Sarno ◽  
Rosalba Petrilli ◽  
Paolo Abondio ◽  
Andrea De Giovanni ◽  
Alessio Boattini ◽  
...  
Keyword(s):  
Southern Italy ◽  
Eastern Mediterranean ◽  
Association Studies ◽  
Specific Gene ◽  
Large Set ◽  
Genome Wide Association Studies ◽  
Mountain Area ◽  
Near Eastern ◽  
Genome Wide

AbstractCalabrian Greeks are an enigmatic population that have preserved and evolved a unique variety of language, Greco, survived in the isolated Aspromonte mountain area of Southern Italy. To understand their genetic ancestry and explore possible effects of geographic and cultural isolation, we genome-wide genotyped a large set of South Italian samples including both communities that still speak Greco nowadays and those that lost the use of this language earlier in time. Comparisons with modern and ancient populations highlighted ancient, long-lasting genetic links with Eastern Mediterranean and Caucasian/Near-Eastern groups as ancestral sources of Southern Italians. Our results suggest that the Aspromonte communities might be interpreted as genetically drifted remnants that departed from such ancient genetic background as a consequence of long-term isolation. Specific patterns of population structuring and higher levels of genetic drift were indeed observed in these populations, reflecting geographic isolation amplified by cultural differences in the groups that still conserve the Greco language. Isolation and drift also affected the current genetic differentiation at specific gene pathways, prompting for future genome-wide association studies aimed at exploring trait-related loci that have drifted up in frequency in these isolated groups.

scholarly journals The ANKS1B gene and its associated phenotypes: focus on CNS drug response

2019 ◽  
Vol 20 (9) ◽  
pp. 669-684
Author(s):  
Rabha M Younis ◽  
Rachel M Taylor ◽  
Patrick M Beardsley ◽  
Joseph L McClay
Keyword(s):  
Drug Response ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Functional Studies ◽  
Genome Wide ◽  
Human Association ◽  
Relevant Variation ◽  
Review Current

The ANKS1B gene was a top finding in genome-wide association studies (GWAS) of antipsychotic drug response. Subsequent GWAS findings for ANKS1B include cognitive ability, educational attainment, body mass index, response to corticosteroids and drug dependence. We review current human association evidence for ANKS1B, in addition to functional studies that include two published mouse knockouts. The several GWAS findings in humans indicate that phenotypically relevant variation is segregating at the ANKS1B locus. ANKS1B shows strong plausibility for involvement in CNS drug response because it encodes a postsynaptic effector protein that mediates long-term changes to neuronal biology. Forthcoming data from large biobanks should further delineate the role of ANKS1B in CNS drug response.

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