HLAは原発性硬化性胆管炎の発症と関連する～日本人集団における疾患感受性HLAアレルの同定～

2025-10-30

2025-10-29 京都大学

京都大学医学研究科の岡本竜弥助教、波多野悦朗教授らの研究チームは、日本人集団における原発性硬化性胆管炎(PSC)の発症に関連するヒト白血球抗原(HLA)アレルを初めて特定した。肝移植を受けたPSC患者と健常対照群のHLAタイピング結果を比較したところ、欧米とは異なる特定アレルが疾患感受性に強く関与していることが明らかになった。また、HLA分子のアミノ酸配列解析により、発症と相関する特定変異部位も同定。これにより、日本人におけるPSCの免疫遺伝的特徴が解明され、診断精度向上や発症メカニズムの理解、個別化治療開発への応用が期待される。成果は『Journal of Hepatology』誌に掲載。

<関連情報>

日本人集団における原発性硬化性胆管炎とHLA-C07:02との関連 Association of Primary Sclerosing Cholangitis With HLA-C07:02 in a Japanese Population

Tatsuya Okamoto, Hideaki Okajima, Masashi Kadohisa, Miki Yamamoto, Elena Yukie Uebayashi, Shinya Okumura, Katsunori Sakamoto, Takashi Ito, Etsuro Hatano
Liver International Published: 23 October 2025
DOI:https://doi.org/10.1111/liv.70376

ABSTRACT

Background and Aims

Primary sclerosing cholangitis (PSC) is a progressive, refractory liver disease often requiring liver transplantation (LT). The association between the disease onset and specific human leukocyte antigen (HLA) typing has been noted, but its relevance in the Japanese population is unknown.

Methods

The HLA 5 locus (HLA-A, B, C, DRB1 and DQB1) 4-digit genotyping results of 31 patients with progressive PSC who underwent LT at our institution were compared to those of 873 healthy Japanese controls.

Results

HLA-B*07:02 (p-corrected [p_c] = 1.9 × 10^-2), HLA-C*07:02 (p_c = 3.9 × 10^-5), HLA-DQB1*05:01 (p_c = 3.7 × 10^-2), and HLA-DRB1*01:01 (p_c = 1.7 × 10^-2) were identified as the susceptibility alleles for PSC. This correlation was stronger in patients with PSC complicated by ulcerative colitis than in those with PSC alone. Furthermore, analyses of the amino acid sequences of each HLA protein revealed that 15 amino acid residues of HLA-C were significantly associated with disease susceptibility (p_c = 1.5 × 10^-4-4.5 × 10^-4).

Conclusions

HLA-C*07:02 is vulnerable to PSC aggravation in the Japanese population.

Summary

HLA-C*07:02 allele was significantly associated with PSC in a Japanese population.
The asociatin was more pronounced in cases in which PSC was complicated by UC.
Amino acid variants of the HLA-C protein were responsible for the Japanese PSC.