Contribution of HLA genes to genetic predisposition in diffuse panbronchiolitis.
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.
Keicho
N
N
Third Department of Internal Medicine, University of Tokyo; Department of Human Genetics, Graduate School of Medical Sciences, University of Tokyo, Japan.
Tokunaga
K
K
Nakata
K
K
Taguchi
Y
Y
Azuma
A
A
Bannai
M
M
Emi
M
M
Ohishi
N
N
Yazaki
Y
Y
Kudoh
S
S
D000483:Alleles; D015415:Biomarkers; D001988:Bronchiolitis / Q000235:genetics*; D016009:Chi-Square Distribution; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D059948:HLA-B44 Antigen; D015236:HLA-C Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D007564:Japan; D008173:Lung Diseases, Obstructive / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
D015415:Biomarkers; D006680:HLA Antigens; D015234:HLA-A Antigens; C082945:HLA-A*33 antigen; D015235:HLA-B Antigens; C105903:HLA-B22 antigen; D059948:HLA-B44 Antigen; C113783:HLA-B54 antigen; D015236:HLA-C Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II