Analysis of HLA-DRB1 polymorphisms in Japanese patients with primary biliary cirrhosis (PBC): The HLA-DRB1polymorphism determines the relative risk of antinuclear antibodies for disease progression in PBC

Minoru Nakamura, Michio Yasunami, Hisayoshi Kondo, Hitomi Horie, Yoshihiro Aiba, Atsumasa Komori, Kiyoshi Migita, Hiroshi Yatsuhashi, Masahiro Ito, Shinji Shimoda, Hiromi Ishibashi

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Abstract

Aims: Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis (PBC). However, the association of human leukocyte antigen (HLA) polymorphisms with these risk factors is unknown. Methods: We determined the HLA-DRB1 genotype in 334 Japanese PBC patients and studied their serum antibodies to gp210 and centromere during the 1-452-month observation period. Results: Anti-gp210 (odds ratio [OR] 46.56, 95% confidence interval [CI], 9.20-850.1) and anti-centromere antibodies (OR, 2.36, 95% CI, 1.28-4.35) were significant risk factors for jaundice- and nonjaundice-type progression, respectively. HLA-DRB1* 0405 and * 0803 predisposed patients to anti-gp210 (OR, 1.61, 95% CI, 1.08-2.39) and anti-centromere (OR, 2.30, 95% CI, 1.41-3.73) antibody production, respectively. HLA-DRB1* 1502 and * 0901 patients were predisposed to nonjaundice-type progression (OR, 1.98, 95% CI, 1.13-3.40 and OR, 1.78, 95% CI, 1.02-3.03), while HLA-DRB1* 0803 and * 0405 patients were predisposed to disease development (OR, 2.24, 95% CI, 1.48-3.41 and OR, 1.53, 95% CI, 1.11-2.11, respectively). Stratifying patients by HLA-DRB1 alleles revealed that anti-gp210 antibodies was a strong risk factor, regardless of the HLA-DRB1 alleles for jaundice-type progression, while anti-centromere antibodies was a significant risk factor for nonjaundice-type progression in patients with HLA-DRB1* 0405 (OR, 6.89, 95% CI, 2.18-26.56) and -DRB1*0803 (OR, 5.42, 95% CI, 1.47-24.62) but not other HLA-DRB1 alleles. Conclusions: HLA-DRB1 polymorphisms are significantly associated with not only disease development and progression but also antinuclear antibody production and the determination of the relative risk of antinuclear antibodies that contribute to PBC disease progression.

Original languageEnglish
Pages (from-to)494-504
Number of pages11
JournalHepatology Research
Volume40
Issue number5
DOIs
Publication statusPublished - May 1 2010

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Biliary Liver Cirrhosis
Antinuclear Antibodies
HLA Antigens
Disease Progression
Odds Ratio
Confidence Intervals
Centromere
Anti-Idiotypic Antibodies
Alleles
Jaundice
Antibody Formation
Genotype
Observation

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Infectious Diseases

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Analysis of HLA-DRB1 polymorphisms in Japanese patients with primary biliary cirrhosis (PBC) : The HLA-DRB1polymorphism determines the relative risk of antinuclear antibodies for disease progression in PBC. / Nakamura, Minoru; Yasunami, Michio; Kondo, Hisayoshi; Horie, Hitomi; Aiba, Yoshihiro; Komori, Atsumasa; Migita, Kiyoshi; Yatsuhashi, Hiroshi; Ito, Masahiro; Shimoda, Shinji; Ishibashi, Hiromi.

In: Hepatology Research, Vol. 40, No. 5, 01.05.2010, p. 494-504.

Research output: Contribution to journalArticle

Nakamura, Minoru ; Yasunami, Michio ; Kondo, Hisayoshi ; Horie, Hitomi ; Aiba, Yoshihiro ; Komori, Atsumasa ; Migita, Kiyoshi ; Yatsuhashi, Hiroshi ; Ito, Masahiro ; Shimoda, Shinji ; Ishibashi, Hiromi. / Analysis of HLA-DRB1 polymorphisms in Japanese patients with primary biliary cirrhosis (PBC) : The HLA-DRB1polymorphism determines the relative risk of antinuclear antibodies for disease progression in PBC. In: Hepatology Research. 2010 ; Vol. 40, No. 5. pp. 494-504.
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title = "Analysis of HLA-DRB1 polymorphisms in Japanese patients with primary biliary cirrhosis (PBC): The HLA-DRB1polymorphism determines the relative risk of antinuclear antibodies for disease progression in PBC",
abstract = "Aims: Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis (PBC). However, the association of human leukocyte antigen (HLA) polymorphisms with these risk factors is unknown. Methods: We determined the HLA-DRB1 genotype in 334 Japanese PBC patients and studied their serum antibodies to gp210 and centromere during the 1-452-month observation period. Results: Anti-gp210 (odds ratio [OR] 46.56, 95{\%} confidence interval [CI], 9.20-850.1) and anti-centromere antibodies (OR, 2.36, 95{\%} CI, 1.28-4.35) were significant risk factors for jaundice- and nonjaundice-type progression, respectively. HLA-DRB1* 0405 and * 0803 predisposed patients to anti-gp210 (OR, 1.61, 95{\%} CI, 1.08-2.39) and anti-centromere (OR, 2.30, 95{\%} CI, 1.41-3.73) antibody production, respectively. HLA-DRB1* 1502 and * 0901 patients were predisposed to nonjaundice-type progression (OR, 1.98, 95{\%} CI, 1.13-3.40 and OR, 1.78, 95{\%} CI, 1.02-3.03), while HLA-DRB1* 0803 and * 0405 patients were predisposed to disease development (OR, 2.24, 95{\%} CI, 1.48-3.41 and OR, 1.53, 95{\%} CI, 1.11-2.11, respectively). Stratifying patients by HLA-DRB1 alleles revealed that anti-gp210 antibodies was a strong risk factor, regardless of the HLA-DRB1 alleles for jaundice-type progression, while anti-centromere antibodies was a significant risk factor for nonjaundice-type progression in patients with HLA-DRB1* 0405 (OR, 6.89, 95{\%} CI, 2.18-26.56) and -DRB1*0803 (OR, 5.42, 95{\%} CI, 1.47-24.62) but not other HLA-DRB1 alleles. Conclusions: HLA-DRB1 polymorphisms are significantly associated with not only disease development and progression but also antinuclear antibody production and the determination of the relative risk of antinuclear antibodies that contribute to PBC disease progression.",
author = "Minoru Nakamura and Michio Yasunami and Hisayoshi Kondo and Hitomi Horie and Yoshihiro Aiba and Atsumasa Komori and Kiyoshi Migita and Hiroshi Yatsuhashi and Masahiro Ito and Shinji Shimoda and Hiromi Ishibashi",
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T1 - Analysis of HLA-DRB1 polymorphisms in Japanese patients with primary biliary cirrhosis (PBC)

T2 - The HLA-DRB1polymorphism determines the relative risk of antinuclear antibodies for disease progression in PBC

AU - Nakamura, Minoru

AU - Yasunami, Michio

AU - Kondo, Hisayoshi

AU - Horie, Hitomi

AU - Aiba, Yoshihiro

AU - Komori, Atsumasa

AU - Migita, Kiyoshi

AU - Yatsuhashi, Hiroshi

AU - Ito, Masahiro

AU - Shimoda, Shinji

AU - Ishibashi, Hiromi

PY - 2010/5/1

Y1 - 2010/5/1

N2 - Aims: Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis (PBC). However, the association of human leukocyte antigen (HLA) polymorphisms with these risk factors is unknown. Methods: We determined the HLA-DRB1 genotype in 334 Japanese PBC patients and studied their serum antibodies to gp210 and centromere during the 1-452-month observation period. Results: Anti-gp210 (odds ratio [OR] 46.56, 95% confidence interval [CI], 9.20-850.1) and anti-centromere antibodies (OR, 2.36, 95% CI, 1.28-4.35) were significant risk factors for jaundice- and nonjaundice-type progression, respectively. HLA-DRB1* 0405 and * 0803 predisposed patients to anti-gp210 (OR, 1.61, 95% CI, 1.08-2.39) and anti-centromere (OR, 2.30, 95% CI, 1.41-3.73) antibody production, respectively. HLA-DRB1* 1502 and * 0901 patients were predisposed to nonjaundice-type progression (OR, 1.98, 95% CI, 1.13-3.40 and OR, 1.78, 95% CI, 1.02-3.03), while HLA-DRB1* 0803 and * 0405 patients were predisposed to disease development (OR, 2.24, 95% CI, 1.48-3.41 and OR, 1.53, 95% CI, 1.11-2.11, respectively). Stratifying patients by HLA-DRB1 alleles revealed that anti-gp210 antibodies was a strong risk factor, regardless of the HLA-DRB1 alleles for jaundice-type progression, while anti-centromere antibodies was a significant risk factor for nonjaundice-type progression in patients with HLA-DRB1* 0405 (OR, 6.89, 95% CI, 2.18-26.56) and -DRB1*0803 (OR, 5.42, 95% CI, 1.47-24.62) but not other HLA-DRB1 alleles. Conclusions: HLA-DRB1 polymorphisms are significantly associated with not only disease development and progression but also antinuclear antibody production and the determination of the relative risk of antinuclear antibodies that contribute to PBC disease progression.

AB - Aims: Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis (PBC). However, the association of human leukocyte antigen (HLA) polymorphisms with these risk factors is unknown. Methods: We determined the HLA-DRB1 genotype in 334 Japanese PBC patients and studied their serum antibodies to gp210 and centromere during the 1-452-month observation period. Results: Anti-gp210 (odds ratio [OR] 46.56, 95% confidence interval [CI], 9.20-850.1) and anti-centromere antibodies (OR, 2.36, 95% CI, 1.28-4.35) were significant risk factors for jaundice- and nonjaundice-type progression, respectively. HLA-DRB1* 0405 and * 0803 predisposed patients to anti-gp210 (OR, 1.61, 95% CI, 1.08-2.39) and anti-centromere (OR, 2.30, 95% CI, 1.41-3.73) antibody production, respectively. HLA-DRB1* 1502 and * 0901 patients were predisposed to nonjaundice-type progression (OR, 1.98, 95% CI, 1.13-3.40 and OR, 1.78, 95% CI, 1.02-3.03), while HLA-DRB1* 0803 and * 0405 patients were predisposed to disease development (OR, 2.24, 95% CI, 1.48-3.41 and OR, 1.53, 95% CI, 1.11-2.11, respectively). Stratifying patients by HLA-DRB1 alleles revealed that anti-gp210 antibodies was a strong risk factor, regardless of the HLA-DRB1 alleles for jaundice-type progression, while anti-centromere antibodies was a significant risk factor for nonjaundice-type progression in patients with HLA-DRB1* 0405 (OR, 6.89, 95% CI, 2.18-26.56) and -DRB1*0803 (OR, 5.42, 95% CI, 1.47-24.62) but not other HLA-DRB1 alleles. Conclusions: HLA-DRB1 polymorphisms are significantly associated with not only disease development and progression but also antinuclear antibody production and the determination of the relative risk of antinuclear antibodies that contribute to PBC disease progression.

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