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.
© 2010 Blackwell Publishing Ltd.