The HLA-DRB1*0301 allele is associated with acute onset of sarcoidosis in the Croatian population

Sarcoidosis is a heterogeneous multisystem granulomatous disease that primarily affects the lungs. A genetic predisposition to sarcoidosis is suggested by different clinical appearances in distinct ethnic groups and family studies. Numerous studies have reported an association of HLA alleles with sarcoidosis, with variation of alleles in different ethnic groups. Therefore, we investigated 142 Croatian sarcoidosis patients attending to the University Hospital for Lung Diseases “ Jordanovac” , Zagreb. Diagnosis was based on the presence of typical clinical features, chest X-ray findings and biopsy evidence of granuloma. One hundred and forty-one unrelated healthy individuals served as controls, all subjects were typed for HLA-DRB1 polymorphism by PCR-SSP method. Analysis of DRB1 alleles between total patients group and controls showed significant differences only for DRB1*0301 allele (p=0.0192). Allele DRB1*0301 was significantly more frequent among patients with acute onset of disease (N=55) in comparison with controls (pcorr=0.013) as well as in the Lofgren sy group (0.0026). Significant association was also observed between acute onset of disease and chronic onset of disease (p=0.047). The distribution of HLA-DRB1 alleles according to the chest X-ray stage showed significantly higher presence of DRB1*0301 allele among patients with chest X-ray stage I (N=57) in comparison to controls (pcorr=0.00533). Allele DRB1*0301 was also significantly more present among patients with pulmonary sarcoidosis than in controls (pcorr=0.00091), while no differences were observed between patients with pulmonary sarcoidosis and patients with systemic disease. The group of treated patients (corticosteroids and/or immunosuppressives) was compared to non-treated. The non-treated group (N=64) showed significantly higher presence of DRB1*0301 allele when compared to controls (pcorr=0.00025). The non-treated group showed significantly lower presence of DRB1*04 allele, compared to the treated group (pcorr= 0.0141) as well as the controls (pcorr=0.0247). In conclusion, our data demonstrated that DRB1*0301 positive patients have higher risk for acute onset of the disease, radiological stage I and Lofgren syndrome.