scholarly journals Genetic Contribution to the Pathogenesis of Primary Biliary Cholangitis

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Satoru Joshita ◽  
Takeji Umemura ◽  
Eiji Tanaka ◽  
Masao Ota
Keyword(s):  
Association Studies ◽  
Disease Onset ◽  
Human Leukocyte ◽  
Primary Biliary Cholangitis ◽  
Cholestatic Liver Disease ◽  
Biliary Cirrhosis ◽  
Genome Wide Association Studies ◽  
Antimitochondrial Antibodies ◽  
Leukocyte Antigen ◽  
Genome Wide

Formerly termed primary biliary cirrhosis, primary biliary cholangitis (PBC) is a chronic and progressive cholestatic liver disease characterized by the presence of antimitochondrial antibodies. Ursodeoxycholic acid (UDCA) therapy is the most effective and approved treatment for PBC and leads to a favorable outcome in the vast majority of cases. Although the etiology of PBC has not yet been elucidated, human leukocyte antigen (HLA) class II alleles have been consistently associated with disease onset for decades. Individuals in different geographic regions of the world may have varying susceptibility alleles that reflect indigenous triggering antigens. In this review, we describe the influence of HLA alleles and other gene polymorphisms on PBC along with the results of genome-wide association studies (GWAS) on this disease.

scholarly journals Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Update: Genetic Pathogenesis

2021 ◽  
Vol 12 ◽  
Author(s):  
Weiran Li ◽  
He Huang ◽  
Minglong Cai ◽  
Tao Yuan ◽  
Yujun Sheng
Keyword(s):  
Association Studies ◽  
Human Leukocyte ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Genome Wide Association Studies ◽  
Leukocyte Antigen ◽  
Anca Associated Vasculitis ◽  
Genome Wide ◽  
Hla Dq ◽  
Genetic And Environmental Factors ◽  
New Biomarkers

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by the inflammation of small and medium vessels and presence of proteinase 3-ANCA or myeloperoxidase-ANCA in the circulation. AAV comprises three clinical subtypes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic GPA (EGPA). Although the pathogenesis of AAV is still unclear, genetic and environmental factors and the immune system are thought to be involved. Genetic factors have been confirmed to play an important role in AAV. Genome-wide association studies have identified numerous genetic variants in MHC and non-MHC regions associated with AAV. The strongest evidence of MHC association in AAV is human leukocyte antigen (HLA)-DP. A significant association between AAV and genetic variations in non-MHC regions, such as CTLA-4, FCGR2A, PTPN22, SERPINA1, and TLR9 has also been found. Moreover, different clinical subtypes of AAV have distinct genetic backgrounds. GPA is associated with HLA-DP1, MPA with HLA-DQ, and EGPA with HLA-DRB4. These findings could help elucidate the etiology of AAV and develop new biomarkers for diagnosis and targeted therapy. Herein, we briefly summarize the updates on the genetic pathogenesis and biomarkers of AAV.

scholarly journals The Genetics of Spondyloarthritis

2020 ◽  
Vol 10 (4) ◽  
pp. 151
Author(s):  
Roberto Díaz-Peña ◽  
Patricia Castro-Santos ◽  
Josefina Durán ◽  
Catalina Santiago ◽  
Alejandro Lucia
Keyword(s):  
Complex Disease ◽  
Inflammatory Diseases ◽  
Association Studies ◽  
Human Leukocyte ◽  
Genome Wide Association Studies ◽  
Leukocyte Antigen ◽  
Genome Wide ◽  
Inflammatory Bowel ◽  
New Treatment

The term spondyloarthritis (SpA) encompasses a group of chronic inflammatory diseases with common features in terms of clinical presentation and genetic predisposition. SpA is characterized by inflammation of the spine and peripheral joints, and is also be associated with extra-articular inflammatory manifestations such as psoriasis, uveitis, or inflammatory bowel disease (IBD). The etiology of SpA is not completely understood, but it is known to have a strong genetic component dominated by the human leukocyte antigen (HLA)-B27. In the last few years, our understanding of genetic susceptibility to SpA, particularly ankylosing spondylitis (AS), has greatly improved thanks to the findings derived from powered genome-wide association studies (GWAS) based on single nucleotide polymorphism (SNP) arrays. These studies have identified many candidate genes, therefore providing new potential directions in the exploration of disease mechanisms, especially with regard to the key role of the immune system in the pathogenesis of SpA. SpA is a complex disease where genetic variability, environmental factors, and random events interact to trigger pathological pathways. The aim of this review is to summarize current findings on the genetics of SpA, some of which might help to study new treatment approaches.

scholarly journals Genes Expression in Type 1 Diabetes: An Update

2019 ◽  
Vol 6 (2) ◽  
pp. 4327-4331
Author(s):  
Dr. Kishore Kumar Soni ◽  
Dr. Sushil Singh
Keyword(s):  
Type 1 Diabetes ◽  
Association Studies ◽  
Disease Onset ◽  
Genome Wide Association Studies ◽  
Autoimmune Destruction ◽  
Disease Biology ◽  
Genome Wide ◽  
Genes Expression ◽  
Practical Effect

Type 1 Diabetes (T1D) is autoimmune disease with a sturdy genetic component, which, through interactions with particular environmental factors, causes disease onset. T1D usually reveals in early to mid-childhood through the autoimmune destruction of pancreatic cells resulting in a lack of insulin production. Traditionally, prior to genome-wide association studies (GWAS), six loci in the genome were fully established to be associated with T1D. The originations of genetic factors involved in T1D through GWAS present the first step in a long process leading to cure. Genes uncovered using this approach is indeed necessary to disease biology and will define the key molecular pathways leading to cure of T1D. However, such genome wide scans can lack coverage in certain regions where it is difficult to , thus, it is possible that other loci with practical effect sizes remain to be uncovered through whole genome sequencing approaches. In this review, we address recent expansions in the genetics of T1D and provide an update on the latest predisposition loci added to the list of genes involved in the of T1D

scholarly journals Genome-Wide Association Studies in Primary Biliary Cirrhosis

2015 ◽  
Vol 35 (04) ◽  
pp. 392-401 ◽  
Author(s):  
Aliya Gulamhusein ◽  
Brian Juran ◽  
Konstantinos Lazaridis
Keyword(s):  
Primary Biliary Cirrhosis ◽  
Association Studies ◽  
Genome Wide Association ◽  
Biliary Cirrhosis ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals Genome‐wide Association Studies of Specific Antinuclear Autoantibody Subphenotypes in Primary Biliary Cholangitis

Hepatology ◽  
2019 ◽  
Vol 70 (1) ◽  
pp. 294-307
Author(s):  
Chan Wang ◽  
Xiaodong Zheng ◽  
Peng Jiang ◽  
Ruqi Tang ◽  
Yuhua Gong ◽  
...  
Keyword(s):  
Association Studies ◽  
Genome Wide Association ◽  
Primary Biliary Cholangitis ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals Tuberculosis Is Not a Risk Factor for Primary Biliary Cirrhosis: A Review of the Literature

2012 ◽  
Vol 2012 ◽  
pp. 1-10
Author(s):  
Daniel S. Smyk ◽  
Dimitrios P. Bogdanos ◽  
Albert Pares ◽  
Christos Liaskos ◽  
Charalambos Billinis ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Primary Biliary Cirrhosis ◽  
Causal Relation ◽  
Association Studies ◽  
Epidemiologic Studies ◽  
High Titre ◽  
Molecular Evidence ◽  
Cholestatic Liver Disease ◽  
Biliary Cirrhosis ◽  
Genome Wide Association Studies

Primary biliary cirrhosis (PBC) is a progressive cholestatic liver disease characterised serologically by cholestasis and the presence of high-titre antimitochondrial antibodies, and histologically by chronic nonsuppurative cholangitis and granulomata. As PBC is a granulomatous disease andMycobacterium tuberculosisis the most frequent cause of granulomata, a causal relation between tuberculosis and PBC has been suggested. Attempts to find serological evidence of PBC-specific autoantibodies such as AMA have been made and, conversely, granulomatous livers from patients with PBC have been investigated for molecular evidence ofMycobacterium tuberculosis. This paper discusses in detail the reported data in support or against an association betweenMycobacterium tuberculosisinfection and PBC. We discuss the immunological and microbiological data exploring the association of PBC with exposure toMycobacterium tuberculosis. We also discuss the findings of large epidemiologic studies investigating the association of PBC with preexistent or concomitant disorders and the relevance of these findings with tuberculosis. Genome-wide association studies in patients with tuberculosis as well as in patients with PBC provide conclusive hints regarding the assumed association between exposure to this mycobacterium and the induction of PBC. Analysis of these data suggest thatMycobacterium tuberculosisis an unlikely infectious trigger of PBC.

Genetic Risk and the Development of Autoimmune Liver Disease

2015 ◽  
Vol 33 (Suppl. 2) ◽  
pp. 13-24 ◽  
Author(s):  
Tom H. Karlsen ◽  
Brian K. Chung
Keyword(s):  
Genetic Risk ◽  
Liver Diseases ◽  
Disease Risk ◽  
Association Studies ◽  
Strong Association ◽  
Human Leukocyte ◽  
Biliary Cirrhosis ◽  
Genome Wide Association Studies ◽  
Autoimmune Liver Diseases ◽  
Study Designs

Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) have collectively been recognized as autoimmune liver diseases. They have all been subjected to genome-wide association studies (GWAS) and several dozens susceptibility loci have been determined. The predominant feature of the genetic findings is that of a strong association with the human leukocyte antigen (HLA) and numerous weak associations scattered throughout the remainder of the genome. The non-HLA associations show some degree of overlap, not only between PBC, PSC and AIH, but also with other autoimmune and immune-mediated diseases. Mathematical modelling shows that the main fraction of autoimmune disease risk (including that of autoimmune liver diseases) is not explained by GWAS, proposing a major role of environmental factors. The HLA associations and autoantibodies observed in these conditions may hold clues as to the nature of such factors, which are exceedingly difficult to map by means of epidemiological study designs. The present review article explores the potential relationship between genetic risk as determined by GWAS and environmental risk in autoimmune liver diseases, and proposes a model for relevant thinking on the susceptibility genes in PBC, PSC and AIH.

scholarly journals STXBP6 and B3GNT6 Genes are Associated With Selective IgA Deficiency

2021 ◽  
Vol 12 ◽  
Author(s):  
Che Kang Lim ◽  
Paola G. Bronson ◽  
Jezabel Varade ◽  
Timothy W. Behrens ◽  
Lennart Hammarström
Keyword(s):  
Risk Allele ◽  
Association Studies ◽  
Immunoglobulin A ◽  
Human Leukocyte ◽  
Iga Deficiency ◽  
Genome Wide Association ◽  
Primary Immune Deficiency ◽  
Genome Wide Association Studies ◽  
Selective Iga Deficiency ◽  
Genome Wide

Immunoglobulin A Deficiency (IgAD) is a polygenic primary immune deficiency, with a strong genetic association to the human leukocyte antigen (HLA) region. Previous genome-wide association studies (GWAS) have identified five non-HLA risk loci (IFIH1, PVT1, ATG13-AMBRA1, AHI1 and CLEC16A). In this study, we investigated the genetic interactions between different HLA susceptibility haplotypes and non-MHC genes in IgAD. To do this, we stratified IgAD subjects and healthy controls based on HLA haplotypes (N = 10,993), and then performed GWAS to identify novel genetic regions contributing to IgAD susceptibility. After replicating previously published HLA risk haplotypes, we compared individuals carrying at least one HLA risk allele (HLA-B*08:01-DRB1*03:01-DQB1*02:01 or HLA-DRB1*07:01-DQB1*02:02 or HLA-DRB1*01-DQB1*05:01) with individuals lacking an HLA risk allele. Subsequently, we stratified subjects based on the susceptibility alleles/haplotypes and performed gene-based association analysis using 572,856 SNPs and 24,125 genes. A significant genome-wide association in STXBP6 (rs4097492; p = 7.63 × 10−9) was observed in the cohort carrying at least one MHC risk allele. We also identified a significant gene-based association for B3GNT6 (PGene = 2.1 × 10–6) in patients not carrying known HLA susceptibility alleles. Our findings indicate that the etiology of IgAD differs depending on the genetic background of HLA susceptibility haplotypes.

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