Analysis of major histocompatibility complex and CTLA‐4 alleles in Brazilian patients with primary biliary cirrhosis

Bittencourt, Paulo Lisboa; Palácios, Selma A.; Farias, Alberto Queiróz; Abrantes-Lemos, Clarice Pires; Cançado, Eduardo Luiz Rachid; Carrilho, Flair José; Laudanna, Antônio Atílio; Kalil, Jorge; Goldberg, Anna Carla

doi:10.1046/j.1440-1746.2003.03091.x

Cited by 40 publications

(44 citation statements)

References 40 publications

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“…54 However, a study from Newcastle, UK did not confirm this alleged association. 15 Similarly, in the data obtained from Scottish, Brazilian, and Chinese series of patients with PBC, 43,55,56 and from a small population of patients undergoing liver transplantation for end-stage PBC, 57 no association of TNF genotypes with disease susceptibility or onset was observed.…”

Section: Mhc and Pbcmentioning

confidence: 92%

“…36 It is possible that positive association might be 41 This association was not confirmed in several other studies from different non-British European populations. 32,35,36,42,43 Moreover, other European studies suggested significant associations of PBC with DR3 29,35 and DPB1*0301, 44 while the most recent study from the United States demonstrated an association between DRB1*08-DQA1*0401-DQB1*04 haplotype and PBC, albeit in a minority of patients. 40 Finally, studies from Japan failed to provide a consistent picture of HLA class II associations with PBC.…”

Section: Mhc and Pbcmentioning

confidence: 97%

“…Accordingly, the coding A49G SNP was found associated with PBC in a large British study 58 and in 77 Chinese patients with PBC, 59 while a smaller study from Brazil failed to confirm the association. 43 Several studied were further dedicated to SNPs of interleukins (IL), based on their active and critical role in the regulation of the immune response. Prompted by experimental data such as its dysregulated production by monocytes in PBC, 60 SNPs of IL-1 were studied in PBC.…”

Section: Mhc and Pbcmentioning

confidence: 99%

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Genes and (auto)immunity in primary biliary cirrhosis

et al. 2005

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Primary biliary cirrhosis (PBC) is a chronic autoimmune cholestatic liver disease most commonly encountered in postmenopausal women; it is characterized by high-titer serum autoantibodies to mitochondrial antigens, elevated serum IgM, progressive destruction of intrahepatic bile ducts, and ultimately liver cirrhosis and failure. The cytopathic mechanisms leading to the selective destruction of intrahepatic cholangiocytes are still largely unknown. The current theory on the pathogenesis of PBC indicated that environmental factors might trigger autoimmunity in genetically susceptible individuals. In fact, genetic predisposition is critical to disease onset and progression, yet peculiar among autoimmune diseases, as indicated by the lack of a strong association with major histocompatibility complex haplotypes. Further, the recently reported concordance rate among monozygotic twins strenghtens the importance of genetic factors, while also indicating that additional factors, possibly infectious agents or xenobiotics, intervene to trigger the disease. In this review, the available data regarding the genetic factors associated with PBC susceptibility and progression, as well as the available evidence regarding the immunomediated pathogenesis of PBC, will be critically illustrated and discussed.

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Section: Mhc and Pbcmentioning

confidence: 92%

Section: Mhc and Pbcmentioning

confidence: 97%

Section: Mhc and Pbcmentioning

confidence: 99%

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Genes and (auto)immunity in primary biliary cirrhosis

et al. 2005

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“…Although early studies found an association between SNP 49G coding and PBC [22][23][24], ensuing reports showed negative relationships with susceptibility [25][26][27][28][29][30] or a positive association with liver damage [31]. A recent investigation reported that rs231725 in the 3'…”

Section: Introductionmentioning

confidence: 99%

Association analysis of cytotoxic T-lymphocyte antigen 4 gene polymorphisms with primary biliary cirrhosis in Japanese patients

Joshita

Umemura

Yoshizawa

et al. 2010

Journal of Hepatology

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“…Early studies of CTLA4 in PBC identified an association with the G allele of 49AG in both UK (69) and Chinese (58) populations, that was not confirmed in a small study from Brazil (31). However, a later study by the UK group which investigated additional SNPs across CTLA4 in an expanded patient population using a more suitable control group, failed to replicate their initial findings of the 49AG association with PBC, calling into question this SNPs relevance to disease (70).…”

Section: "Autoimmune" Genesmentioning

confidence: 98%

Genetics and Genomics of Primary Biliary Cirrhosis

Juran

Lazaridis

2008

Clinics in Liver Disease

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The etiological and pathogenic factors contributing to PBC development, progression, response to treatment, and ultimately, outcome remain a mystery. This lack of knowledge can be attributed to the complexity of PBC, wherein a number of environmental triggers may be culpable, but require coexisting genetic susceptibility to exert their effect. Recognition of the genomic regions harboring these heritable risk factors has been hindered by the rarity and late onset of PBC, which has rendered the collection of adequate numbers of patients and family members for genetic analyses a difficult task. Recent advancements in the discipline of genomics holds promise to fundamentally change our understanding, prevention, and therapy of PBC. This chance arises from the development of new high-throughput approaches to genotyping, providing the means to rapidly uncover many of the genetic polymorphisms that are relevant to disease. In order to move ahead, large registries and biospecimen repositories of patients with PBC, their family members, and well-matched controls need to be established, maintained, and continually expanded. At the same time, sizeable, comprehensive haplotype mapping based association studies of functionally plausible candidate gene groups (e.g. immune function genes) as well as more far reaching genome-wide association studies will be necessary to form the basis upon which the genetic predisposition to PBC can be defined. This first set of experimental data will provide the means for future fine mapping studies, resequencing efforts, functional experimentation, and elucidation of gene-environment and gene-gene interaction; perhaps paving new paths in PBC research.

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Analysis of major histocompatibility complex and CTLA‐4 alleles in Brazilian patients with primary biliary cirrhosis

Abstract: Susceptibility to PBC in Brazil is not associated with HLA-DR and DQ antigens and CTLA-4 genotypes. TNFA alleles were not shown to influence disease progression.

Cited by 40 publications

References 40 publications

Genes and (auto)immunity in primary biliary cirrhosis

Genes and (auto)immunity in primary biliary cirrhosis

Association analysis of cytotoxic T-lymphocyte antigen 4 gene polymorphisms with primary biliary cirrhosis in Japanese patients

Genetics and Genomics of Primary Biliary Cirrhosis

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