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Am. J. Respir. Crit. Care Med., Volume 158, Number 3, September 1998, 846-850

Contribution of HLA Genes to Genetic Predisposition in Diffuse Panbronchiolitis

NAOTO KEICHO, KATSUSHI TOKUNAGA, KOICHIRO NAKATA, YOSHIO TAGUCHI, ARATA AZUMA, MAKOTO BANNAI, MITSURU EMI, NOBUYA OHISHI, YOSHIO YAZAKI, and SHOJI KUDOH

Third Department of Internal Medicine, University of Tokyo; Department of Human Genetics, Graduate School of Medical Sciences, University of Tokyo; Division of Respiratory Diseases, Toranomon Hospital; Department of Respiratory Medicine, Tenri Hospital; Fourth Department of Internal Medicine, Nippon Medical School; Department of Research, Japanese Red Cross Tokyo Metropolitan Blood Center; and Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Tokyo, Japan

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 (chi 2 = 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.




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