A BTNL2 gene variant confers to sarcoidosis susceptibility by an increased risk towards the chronic form of the disease

Introduction: Sarcoidosis is an inflammatory granulomatous disorder that primarily affects lungs and lymph nodes. Recently, a significant association of sarcoidosis with a frequent SNP in the BTNL2 gene, rs2076530, was described in a German sarcoidosis sample. BTNL2 is a member of the immunoglobulin gene family and is related to CD80 and CD86 co-stimulatory receptors, although its exact function is unknown. No replication of the BTNL2 rs2076530 susceptibility to sarcoidosis has yet been done in an independent German case-control study. We therefore performed a case-control association study including 210 patients with sarcoidosis and 202 controls. Methods: Genotyping of rs207653 was performed using Taqman technique. Results: The genotype distributions in the cohort were in accordance with the Hardy-Weinberg equilibrium. The A-allele frequency of rs2076530 was significantly increased in sarcoidosis patients compared to controls (A=0.6929, G=0.3071 in cases and A=0.6188, G=0.3812 in controls). It was significantly associated with an increased risk of sarcoidosis in co-dominant and dominant models (OR=2.31 (1.27–4.23); P<0.006, table 1), but not in a recessive model (p=0.276). The calculated population attributable risk (PAR) for AA homozygotes and AG heterozygotes was 34.6%. Our results were in accordance with the reported association between BTNL2 and sarcoidosis and replicated the finding that A-allele carrier of rs2076530 have a more than two-fold increased risk to develop sarcoidosis compared to GG homozygotes in German population. In addition, we tested, whether this increased risk is present in both, chronic and acute forms of sarcoidosis. Interestingly, we found the chronic form significantly associated with the A-allele in co-dominant and dominant models (OR=2.87 (1.29–6.42); P<0.0069, table 1), but not the acute form, with a population attributable risk (PAR) for AA homozygotes and AG heterozygotes of 50%. Discussion: This study underlines the importance of the association of BTNL2 rs2076530 variant with the susceptibility to sarcoidosis in a German population and furthermore our data suggests that susceptibility is preferentially towards the chronic form of the disease.