Contribution of HLA Genes to Genetic Predisposition in Diffuse Panbronchiolitis

• Published in: American journal of respiratory and critical care medicine Vol. 158; no. 3; pp. 846 - 850
• Main Authors: KEICHO, NAOTO, TOKUNAGA, KATSUSHI, NAKATA, KOICHIRO, TAGUCHI, YOSHIO, AZUMA, ARATA, BANNAI, MAKOTO, EMI, MITSURU, OHISHI, NOBUYA, YAZAKI, YOSHIO, KUDOH, SHOJI
• Format: Journal Article
• Language: English
• Published: New York, NY American Lung Association 01.09.1998
• Subjects: Alleles; Biological and medical sciences; Biomarkers; Bronchiolitis - genetics; Chi-Square Distribution; Chronic obstructive pulmonary disease, asthma; Female; Genetic Linkage - genetics; Genetic Predisposition to Disease; Genotype; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class II - genetics; 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; Humans; Japan; Lung Diseases, Obstructive - genetics; Male; Medical sciences; Middle Aged; Molecular Structure; Pneumology; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Asia; Japan; Diffuse; Human; HLA-System; Respiratory disease; HLA-DR-System; Major histocompatibility system; Class II histocompatibility antigen; Exploration; Genetic determinism; Bronchiolitis; Polymerase chain reaction; Allele; Obstructive pulmonary disease; Class I histocompatibility antigen
• ISSN: 1073-449X; 1535-4970
• 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.