Primary sclerosing cholangitis in genetically diverse populations listed for liver transplantation: unique clinical and human leukocyte antigen associations

Liver Transpl. 2010 Nov;16(11):1324-30. doi: 10.1002/lt.22161.

Abstract

Primary sclerosing cholangitis (PSC) is well characterized in European populations. We aimed to characterize clinical characteristics and human leukocyte antigen (HLA) associations in a population of European American, Hispanic, and African American PSC patients listed for liver transplantation (LT). Population-stratified demographic, clinical, and HLA data from 6767 LT registrants of the United Network for Organ Sharing who had a diagnosis of PSC (4.7% of the registrants) were compared to data from registrants with other diagnoses. Compared to European Americans and Hispanics, African Americans were significantly younger (46.6 ± 13.7, 42.3 ± 15.9, and 39.7 ± 13.1 years, respectively; P = 0.002) and were listed with a higher Model for End-Stage Liver Disease score (15.2 ± 7.5, 14.9 ± 7.6, and 18.1 ± 9.3, respectively; P = 0.001); they were also less frequently noted to have inflammatory bowel disease in comparison with European Americans (71.4% versus 60.5%, P < 0.01). In multivariate analysis, African origin was a significant factor associated with listing for LT with PSC (odds ratio with respect to European Americans = 1.325, 95% confidence interval = 1.221-1.438). HLA associations in European Americans, Hispanics, and African Americans with PSC versus alcoholic liver disease were detected for HLA-B8, HLA-DR13, and protective HLA-DR4. However, HLA-DR3, which is in linkage disequilibrium with HLA-B8, showed associations only in European Americans and Hispanics. In conclusion, African Americans with PSC who are listed for LT differ clinically from European Americans and Hispanics. The association with HLA-B8 but not HLA-DR3 in African Americans should make possible the refinement of the HLA associations in PSC.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Age Factors
  • Alleles
  • Case-Control Studies
  • Cholangitis, Sclerosing* / complications
  • Cholangitis, Sclerosing* / ethnology
  • Cholangitis, Sclerosing* / genetics
  • Cholangitis, Sclerosing* / immunology
  • Colitis, Ulcerative / etiology
  • Colitis, Ulcerative / genetics
  • Colitis, Ulcerative / immunology
  • Ethnicity*
  • Female
  • Genetic Predisposition to Disease* / ethnology
  • Genetic Variation
  • HLA-B8 Antigen / genetics
  • HLA-B8 Antigen / immunology
  • HLA-DR Antigens / genetics
  • HLA-DR Antigens / immunology
  • Haplotypes
  • Histocompatibility Testing
  • Humans
  • Inflammatory Bowel Diseases / etiology
  • Inflammatory Bowel Diseases / genetics
  • Inflammatory Bowel Diseases / immunology
  • Linkage Disequilibrium
  • Liver Diseases / complications
  • Liver Diseases / genetics
  • Liver Diseases / immunology
  • Liver Diseases / surgery
  • Liver Transplantation* / immunology
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis

Substances

  • HLA-B8 Antigen
  • HLA-DR Antigens