Association of Primary Sclerosing Cholangitis With HLA-C*07:02 in a Japanese Population.

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 [pc] = 1.9 × 10-2), HLA-C*07:02 (pc = 3.9 × 10-5), HLA-DQB1*05:01 (pc = 3.7 × 10-2), and HLA-DRB1*01:01 (pc = 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 (pc = 1.5 × 10-4-4.5 × 10-4).

CONCLUSIONS

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