HLA genes and sarcoidosis across three populations: Greeks, Czechs, and Koreans

<bold>Background:</bold> Studies of associations between sarcoidosis and HLA, the most polymorphic immune system, focus on patients of distinct ethnic origins. Therefore, we present HLA analyses in sarcoid patients from 3 populations. <bold>Methods:</bold> Czech (n=310), Korean (103) and Greek (103) sarcoidosis patients diagnosed according to international guidelines were enrolled. HLA was determined at allele level by Next Generation Sequencing. <bold>Results:</bold> Both shared and single population-specific associations emerged from the analyses. Shared associations were exemplified by a higher disease risk for HLA-DRB1*14:54 allele in all 3 populations, or by a strong protective effect of HLA-DQA1*05:01 allele against sarcoidosis in Greeks and Koreans. Population-specific associations were observed when comparing profiles in disease phenotypes, e.g. HLA-DRB1*11:01 was a risk factor for advanced chest-X-ray stages in Czechs. While many associations between HLA and sarcoidosis revealed by precise HLA-typing have been already reported using lower-resolution methods, our study brings novel findings, specifically from the Greek cohort. There, a strong association between HLA-DQB1*06:03 and sarcoidosis risk (5-fold) was detected. By contrast, a strong protective effect of HLA-DRB1*11:04 was shown, this was never reported in sarcoidosis. <bold>Conclusion:</bold> Our study aligns with the approach to investigating sarcoidosis genetics in ethnically distinct populations. Observed new and population-specific associations should be verified in extended replication cohorts. Further, results can be used in metanalyses of sarcoidosis immunogenetic data to extend the knowledge of shared risk/protective factors for sarcoidosis and its phenotypes across ethnicities.