Susceptibility to primary biliary cirrhosis is associated with human leukocyte antigen DRB10803 in Japanese patients

Oguri, Hikaru; Oba, Sakae; Ogino, Hidero; Inagaki, Yutaka; Kaneko, Shuichi; Unoura, Masashi; Kobayashi, Kenichi

doi:10.1016/0928-4346(94)90061-2

Cited by 17 publications

(4 citation statements)

References 17 publications

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“…Among these, only HLA has consistently been associated with PBC susceptibility 15. The HLA‐ DRB1*08 family of alleles has been the most frequently described determinant for susceptibility to PBC16–21; HLA‐ DRB1*08:03 has been associated with PBC in the Japanese 22–26. However, HLA DQB1 alleles and haplotypes have not been fully investigated, and large cohort studies have indicated that HLA‐ DRB1*11 and DRB1*13 alleles are, in fact, protective against PBC 20, 21, 26.…”

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confidence: 99%

Human Leukocyte Antigen Class II Molecules Confer Both Susceptibility and Progression in Japanese Patients With Primary Biliary Cirrhosis

et al. 2012

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Along with twin and family studies, recent genome-wide association studies suggest that genetic factors contribute to the susceptibility and severity of primary biliary cirrhosis (PBC). Although several reports have demonstrated that the human leukocyte antigen (HLA) DRB1*08:03 allele is associated with disease susceptibility in Japan, the precise analysis of HLA haplotypes and the role of amino acid alignment have not been fully clarified. We investigated HLA class I A, B, and C and HLA class II DRB1 and DQB1 alleles and haplotypes in 229 Japanese patients with PBC and compared them with the published data of 523 healthy subjects. Significant associations were found with PBC susceptibility for the DRB1*08:03-DQB1*06:01 (13% versus 6%; P 5 0.000025; odds ratio [OR] 5 2.22) and DRB1*04:05-DQB1*04:01 haplotypes (17% versus 13%; P 5 0.044; OR 5 1.38). Conversely, there were significant protective associations with the DRB1*13:02-DQB1*06:04 (2% versus 5%; P 5 0.00093; OR 5 0.27) and DRB1*11:01-DQB1*03:01 haplotypes (1% versus 4%; P 5 0.03; OR 5 0.37). The frequency of the DRB1*09:01-DQB1*03:03 haplotype was significantly higher in patients who had received orthotopic liver transplantation (33% versus 11%; P 5 0.0012; OR 5 3.96). Furthermore, the frequency of serine at position 57 (P 5 0.0000015; OR 5 1.83) of the DRbchain differed the most in patients with PBC, compared with healthy subjects. Conclusion: This study established the role of HLA haplotypes in determining PBC susceptibility and progression in the Japanese population. Further resequencing of the HLA region is required to more precisely identify the genetic components of PBC. (HEPATOLOGY 2012;55:506-511)

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confidence: 99%

Human Leukocyte Antigen Class II Molecules Confer Both Susceptibility and Progression in Japanese Patients With Primary Biliary Cirrhosis

et al. 2012

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“…Once the variable encoding this effect had been included as a covariate in the regression model, the next most associated amino acid ( P = 1.73x10 -39 ) was residue L at position 74 of HLA-DRβ1. HLA-DRβ1 74L was previously identified as significantly associated with PBC by Donaldson et al [1] and Invernizzi et al [22], as well as by an earlier small Japanese study (53 PBC patients and 60 controls) [5]. This substitution occurs both on classical alleles HLA-DRB1*08 : 01 (which is strongly associated with PBC in Europeans) and on HLA-DRB1*08 : 03 (which is known to be associated with PBC in Japanese/Chinese populations [4, 5, 25] and thus offers a potential explanation for the HLA-DRB1*08 associations seen in these different populations.…”

Section: Resultsmentioning

confidence: 99%

“…HLA-DRβ1 74L was previously identified as significantly associated with PBC by Donaldson et al [1] and Invernizzi et al [22], as well as by an earlier small Japanese study (53 PBC patients and 60 controls) [5]. This substitution occurs both on classical alleles HLA-DRB1*08 : 01 (which is strongly associated with PBC in Europeans) and on HLA-DRB1*08 : 03 (which is known to be associated with PBC in Japanese/Chinese populations [4, 5, 25] and thus offers a potential explanation for the HLA-DRB1*08 associations seen in these different populations. Our identification of amino acids in HLA-DPβ1 and HLA-DRβ1 as the top contributors to HLA-induced PBC risk is consistent with the results of Invernizzi et al [22] who found in their (much smaller) Italian data set that conditioning on residue L at position 11 of HLA-DPβ1 largely removed the signal at HLA-DPB1 , and who noted that, considered together, HLA-DRB1*08 and HLA-DPB1*03 : 01 accounted for the majority of the signal in the HLA region.…”

Section: Resultsmentioning

confidence: 99%

Amino acid residues in five separate HLA genes can explain most of the known associations between the MHC and primary biliary cholangitis

et al. 2018

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Primary Biliary Cholangitis (PBC) is a chronic autoimmune liver disease characterised by progressive destruction of intrahepatic bile ducts. The strongest genetic association is with HLA-DQA1*04:01, but at least three additional independent HLA haplotypes contribute to susceptibility. We used dense single nucleotide polymorphism (SNP) data in 2861 PBC cases and 8514 controls to impute classical HLA alleles and amino acid polymorphisms using state-of-the-art methodologies. We then demonstrated through stepwise regression that association in the HLA region can be largely explained by variation at five separate amino acid positions. Three-dimensional modelling of protein structures and calculation of electrostatic potentials for the implicated HLA alleles/amino acid substitutions demonstrated a correlation between the electrostatic potential of pocket P6 in HLA-DP molecules and the HLA-DPB1 alleles/amino acid substitutions conferring PBC susceptibility/protection, highlighting potential new avenues for future functional investigation.

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“…HLA-DR8 was included because increased frequency has been reported to be associated with PBC in both Caucasian and Japanese patients. 27,28 Although positive ANA was scored as Ϫ1, PBC-specific ANA, such as anti-centromere antibody (ACA), anti-Sp100, or anti-gp210 was scored as ϩ2.…”

Section: Scoring Systemmentioning

confidence: 99%

A scoring system for primary biliary cirrhosis and its application for variant forms of autoimmune liver disease

Yamamoto

Terada

Okamoto

et al. 2003

Journal of Gastroenterology

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Susceptibility to primary biliary cirrhosis is associated with human leukocyte antigen DRB10803 in Japanese patients

Cited by 17 publications

References 17 publications

Human Leukocyte Antigen Class II Molecules Confer Both Susceptibility and Progression in Japanese Patients With Primary Biliary Cirrhosis

Human Leukocyte Antigen Class II Molecules Confer Both Susceptibility and Progression in Japanese Patients With Primary Biliary Cirrhosis

Amino acid residues in five separate HLA genes can explain most of the known associations between the MHC and primary biliary cholangitis

A scoring system for primary biliary cirrhosis and its application for variant forms of autoimmune liver disease

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