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The  HLA class II  ( DRB1  and  DQB1 ) associations with sarcoidosis have been studied by several groups but often without consistent results. In this paper, we consider the hypothesis that observed inconsistencies relate to distinct, genetically encoded disease phenotypes which differ in prevalence between centres. We therefore typed  HLA-DRB1  and  DQB1  in 340 UK, 139 Dutch and 163 Japanese sarcoidosis patients and, respectively, 354, 218 and 168 healthy controls from these populations. We applied consistent phenotyping and genotyping and investigated associations between  HLA class II  alleles and distinct disease phenotypes within and between ethnic groups.  DRB1*01  and  DQB1*0501  are protective against all manifestations of sarcoidosis. Lung-predominant sarcoidosis is associated with  DRB1*12  and  *14 . Löfgren's syndrome is a common sarcoidosis phenotype in the Dutch and is strongly associated with the  DRB1*0301  allele. This phenotype is not seen among the Japanese in whom  DRB1*0301  is absent. The same allele is protective for UK uveitis. Sarcoid uveitis is common in Japan. The  DRB1*04–DQB1*0301  haplotype is a risk factor for this disease manifestation in Japanese and UK subjects but protective for sarcoidosis overall. We show that distinct sarcoidosis phenotypes have similar genetic associations across ethnic groups. The disease case mix differs between centres and may be explained by different ethnic allelic frequencies.

Sarcoidosis HLA class II genotyping distinguishes differences of clinical phenotype across ethnic groups