BTNL2 gene polymorphism associations with susceptibility and phenotype expression in sarcoidosis

A functional polymorphism within butyrophilin-like 2 (BTNL2) gene has been described as a potential risk factor for sarcoidosis. The association between chronicity and the rs2076530 SNP A allele has also been reported. This study evaluates the BTNL2 rs2076530 G/A allele associations with sarcoidosis susceptibility and disease evolution in a Portuguese cohort of patients. A case-control study of 151 patients and 150 controls was performed. Allele frequencies were compared with Chi-square test in a univariate analysis and with logistic regression in a multivariate analysis. BTNL2 rs206530 A allele frequencies were significantly higher in sarcoidosis with no linkage disequilibrium with HLA-DRB1 alleles, except in the subgroup of patients with Löfgren syndrome where the determinant allele was HLA-DRB1*03. The A allele was also increased in those with isolated thoracic disease, with no differences regarding radiological stages or disease evolution. HLA-DRB1*03, besides the association with Löfgren syndrome was significantly related with disease resolution. Our data confirms the association of BTNL2 rs2076530 A allele with sarcoidosis susceptibility in a Portuguese population. We found independent genetic risk factors in clinically distinct disease phenotypes: BTNL2 rs2076530 A allele in patients without Löfgren syndrome or with isolated thoracic disease, and HLA-DRB1*03 in Löfgren syndrome or disease resolution.