title: Severe pulmonary sarcoidosis is strongly associated with the haplotype HLA-DQB1*0602-DRB1*150101.
abstract: Sarcoidosis is a multiorgan granulomatous disease of unknown etiology. Several lines of evidence suggest a genetic predisposition and associations have been demonstrated with HLA antigens. HLA-DQB1 has been proposed as one of the candidate genes. To investigate the relationship between DQB1 and sarcoidosis at the allele level, we typed 149 Dutch Caucasian sarcoidosis patients for DQB1 by sequence-based typing as the ultimate technique to identify all DQB1 alleles. Phenotype frequencies were compared with controls. Both groups were also typed for HLA-A, -B, and -DRB1 at the low-resolution level. To decide on the possible linkage with DR, all DRB1*15-positive patients were subsequently sequence-based typed. Results showed a statistically significant increase of DQB1*0602 in sarcoidosis patients. The increase was also proven for DRB1*150101. Because of the high linkage disequilibrium between DRB1*1501 and DQB1*0602 in Caucasians, it could not be decided which one was the primary association. The increase was most pronounced in patients with severe pulmonary sarcoidosis indicated by radiographic stages II-IV. Although not statistically significant, DRB1*03 and DQB1*0201 were increased in radiographic stage I compared with II-IV. This study provides evidence that the combination DQB1*0602/DRB1*150101 is a strong positive marker for severe pulmonary sarcoidosis.
authors.affiliation: Tissue Typing Laboratory, University Hospital Maastricht, Maastricht, The Netherlands.
authors.forename: Christina E M
authors.initials: CE
authors.lastname: Voorter
authors.forename: Marjolein
authors.initials: M
authors.lastname: Drent
authors.forename: Ella M
authors.initials: EM
authors.lastname: van den Berg-Loonen
mesh_terms: D000328:Adult; D005260:Female; D005787:Gene Frequency; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D013902:Radiography, Thoracic; D017565:Sarcoidosis, Pulmonary / Q000145:classification / Q000235:genetics* / Q000473:pathology
chemical_list: D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D008562:Membrane Glycoproteins