The BTNL2 A allele variant is frequent in Danish patients with sarcoidosis

Background: The butyrophilin‐like 2 (BTNL2) gene is located on chromosome 6p21.3 close to the HLA‐class II genes. An association has been reported between sarcoidosis and a single nucleotide polymorphism in BTNL2, rs2076530, also termed the A allele. Objectives: To evaluate whether patients with sarcoidosis carry the A allele more frequently than healthy subjects. Methods: The series comprised 87 ethnic Danes with sarcoidosis and 113 healthy control subjects. Analysis of rs2076530 was performed by Taqman assay, polymerase chain reaction and sequencing of genomic DNA. Results: Sarcoidosis patients had a higher frequency of the A allele than controls (73.9% vs 55.8%) (P < 0.025). The frequency of GG, GA and AA genotype was 5.7%, 40.2% and 54.0% in patients vs 16.0%, 56.6% and 27.4% in controls (P < 0.001). The AA genotype was associated with increased risk of sarcoidosis in both a dominant [odds ratio (OR) 3.1; 95% confidence interval (CI) 1.1–8.7; P < 0.03] and a recessive model (OR 3.1; 95% CI 1.72–5.61; P < 0.001). Population attributable fraction for disease was 50% in a dominant model and 25% in a recessive model. Conclusions: The BTNL2 A allele variant occurs with a high frequency in Danish patients with sarcoidosis and the AA genotype is associated with a ～threefold higher risk of sarcoidosis than the GG genotype. Our results should encourage future studies on the interrelationship between the BTNL2 protein and granuloma formation in sarcoidosis. Please cite this paper as: Milman N, Svendsen CB, Nielsen FC and Hansen TvO. The BTNL2 A allele variant is frequent in Danish patients with sarcoidosis. Clin Respir J 2011; 5: 105–111.