Lack of association between the CARD10 rs6000782 polymorphism and type 1 autoimmune hepatitis in a Japanese population

Migita, Kiyoshi; Jiuchi, Yuka; Furukawa, Hiroshi; Nakamura, Minoru; Komori, Atsumasa; Yasunami, Michio; Kozuru, Hideko; Abiru, Seigo; Yamasaki, Kazumi; Nagaoka, Shinya; Hashimoto, Satoru; Bekki, Shigemune; Yoshizawa, Kaname; Shimada, Muneaki; Kouno, Hiroshi; Kamitsukasa, Hiroshi; Komatsu, Tatsuji; Hijioka, Taizo; Nakamuta, Makoto; Naganuma, Atsushi; Yamashita, Haruhiro; Nishimura, Hideo; Ohta, Hiroyuki; Nakamura, Yoko; Ario, Keisuke; Oohara, Yukio; Sugi, Kazuhiro; Tomizawa, M.; Sato, Takeaki; Takahashi, H.; Muro, Toyokichi; Makita, Fujio; Mita, Eiji; Sakai, Hironori; Yatsuhashi, Hiroshi

doi:10.1186/s13104-015-1733-4

Cited by 10 publications

(4 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The rs3184504*A allele of the Src homology 2‐B adaptor protein 3 gene ( SH2B3 ) has been associated with the disease in northern European patients , and its gene product may affect the coordination of signalling events that influence cell migration, inflammatory activity and T lymphocyte activation . Like the loci within the MHC, the risk‐laden loci outside the MHC lack disease specificity and demonstrate variability between ethnic groups .…”

Section: Introductionmentioning

confidence: 99%

Epigenetic changes and their implications in autoimmune hepatitis

Czaja

2018

Eur J Clin Investigation

View full text Add to dashboard Cite

Background: The genetic risk of autoimmune hepatitis is insufficient to explain the observed risk, and epigenetic changes may explain disparities in disease occurrence in different populations within and between countries. The goal of this review was to examine how epigenetic changes induced by the environment or inherited as a phenotypic trait may affect autoimmune hepatitis and be amenable to therapeutic intervention. Materials and methods: Pertinent abstracts were identified in PubMed by multiple search terms. The number of abstracts reviewed was 1689, and the number of full-length articles reviewed exceeded 150. Results: Activation of pro-inflammatory genes in autoimmune disease is associated with hypomethylation of deoxyribonucleic acid and modification of histones within chromatin. Organ-specific microribonucleic acids can silence genes by marking messenger ribonucleic acids for degradation, and they can promote inflammatory activity or immunosuppression. High circulating levels of the microribonucleic acids 21 and 122 have been demonstrated in autoimmune hepatitis, and they may increase production of pro-inflammatory cytokines. Microribonucleic acids are also essential for maintaining regulatory T cells. Drugs, pollutants, infections, diet and ageing can induce inheritable epigenetic changes favouring autoimmunity. Reversal is feasible by manipulating enzymes, transcription factors, gene-silencing molecules and toxic exposures or by administering methyl donors and correcting vitamin D deficiency. Gene targets, site specificity, efficacy and consequences are uncertain. Conclusions: Potentially reversible epigenetic changes may affect the occurrence and outcome of autoimmune hepatitis, and investigations are warranted to determine the nature of these changes, key genomic targets, and feasible interventions and their consequences.

show abstract

Section: Introductionmentioning

confidence: 99%

Epigenetic changes and their implications in autoimmune hepatitis

Czaja

2018

Eur J Clin Investigation

View full text Add to dashboard Cite

show abstract

“…The previous GWAS on European type 1 AIH also suggested associations of SNVs in HLA , CARD10 , SH2B3 , and ICOS [ 34 ]. The association between rs6000782 in CARD10 and AIH was not observed in a replication study in Japanese populations [ 80 ]. CARD10 is a scaffold protein and plays a critical role in the activation of the nuclear factor-κB (NF-κB) pathway [ 81 ].…”

Section: Non- Hla Genesmentioning

confidence: 99%

Genetic risk factors for autoimmune hepatitis: implications for phenotypic heterogeneity and biomarkers for drug response

et al. 2021

Self Cite

View full text Add to dashboard Cite

Autoimmune hepatitis (AIH) is a rare chronic progressive liver disease with autoimmune features. It mainly affects middle-aged women. AIH is occasionally complicated with liver cirrhosis that worsens the prognosis. Genetic and environmental factors are involved in the pathogenesis of AIH. Genetic studies of other diseases have been revealing of pathogenesis and drug efficacy. In this review, we summarize the genetic risk factors for AIH, including human leukocyte antigen (HLA) and non-HLA genes. A genome-wide association study (GWAS) on European AIH revealed the strongest associations to be with single nucleotide variants (SNVs) in HLA. Predisposing alleles for AIH were DRB1*03:01 and DRB1*04:01 in Europeans; DRB1*04:04, DRB1*04:05, and DRB1*13:01 in Latin Americans; and DRB1*04:01 and DRB1*04:05 in Japanese. Other risk SNVs in non-HLA genes for AIH were found by a candidate gene approach, but several SNVs were confirmed in replication studies. Some genetic factors of AIH overlapped with those of other autoimmune diseases. Larger-scale GWASs of other ethnic groups are required. The results of genetic studies might provide an explanation for the phenotypic heterogeneity of AIH and biomarkers for drug responses.

show abstract

“…Another challenge is to distinguish between differences related to risk‐laden genes that differ because of ethnicity and those that differ because of cohort selection, detection method and statistical power. GWAS in northern European patients have suggested a possible association of the r36000782 allele of the caspase recruitment domain family member 10 (CARD10) gene with autoimmune hepatitis ( P = 3.0 × 10 −6 ), whereas a multicentre cohort study in Japan based on a polymerase chain reaction‐restriction length polymorphism method (PCR‐RFLP) disclosed no association ( P = .38) . Similar discordant observations between ethnically diverse cohorts have been described for polymorphisms of the cytotoxic T lymphocyte antigen‐4 ( CTLA‐4 ) gene and the tumour necrosis factor ( TNF ) gene …”

Section: Resultsmentioning

confidence: 69%