Contribution of HLA genes to genetic predisposition in diffuse panbronchiolitis

Am J Respir Crit Care Med. 1998 Sep;158(3):846-50. doi: 10.1164/ajrccm.158.3.9712125.


Diffuse panbronchiolitis (DPB) in East Asia is a distinctive chronic obstructive pulmonary disease of unknown etiology. We hypothesize that the disease susceptibility is due to genetic predisposition unique to Asians. Association between human leukocyte antigen (HLA)-Bw54 and the disease was previously reported. In the present study, using newly developed polymerase chain reaction (PCR)- based methods, we directly analyzed HLA class I and II alleles in 76 Japanese patients. HLA-A, -B, and -C antigens were screened by the conventional typing method, and then B22-group alleles including HLA-B54 were genotyped by single-strand conformation polymorphism analysis. Alleles of HLA-DRB1 gene were fully determined by the microtiter plate hybridization method. Thirty-seven percent of the patients possessed HLA-B*5401 allele conserved predominantly in East Asians, as compared with 15% of 110 healthy volunteers (chi2 = 12.4, p = 0.0004). In addition, 4% of the patients possessed B*5504 also unique to Asians but a rare allele which was not found in normal control subjects in this study. Typing of HLA-DRB1 class II gene did not demonstrate strong positive association with the disease. A33, B44, and DRB1*1302 showed negative association with the disease. We conclude that distinctive molecular structure of HLA-B alleles or a closely linked gene in the HLA region contributes to genetic predisposition in diffuse panbronchiolitis. This may partly explain why this disorder is found primarily in Asians.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Biomarkers
  • Bronchiolitis / genetics*
  • Chi-Square Distribution
  • Female
  • Genetic Linkage / genetics
  • Genetic Predisposition to Disease
  • Genotype
  • HLA Antigens / genetics*
  • HLA-A Antigens / genetics
  • HLA-B Antigens / genetics
  • HLA-B44 Antigen
  • HLA-C Antigens / genetics
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class II / genetics
  • Humans
  • Japan
  • Lung Diseases, Obstructive / genetics
  • Male
  • Middle Aged
  • Molecular Structure
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational


  • Biomarkers
  • HLA Antigens
  • HLA-A Antigens
  • HLA-A*33 antigen
  • HLA-B Antigens
  • HLA-B22 antigen
  • HLA-B44 Antigen
  • HLA-B54 antigen
  • HLA-C Antigens
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II