Abstract

Objective: The HLA region encodes numerous immune response genes, with the DR/DQ molecules consistently associated with autoimmune disease (AID). Recent studies in sarcoidosis have identified association of a single nucleotide polymorphism (SNP) rs2076530 within BTNL2, a potential T-cell inhibitor, independent of the known DRB1 association. The aim of this study was to investigate the association rs2076530 with disease in a large UK Caucasian Graves' disease (GD) dataset. Design: A case control association study of the rs2076530 polymorphism. Patients: Eight hundred sixty-four Graves' disease patients and 864 controls. Measurements: Tests for association with disease. Results: We detected association of rs2076530 within a large GD dataset OR = 1·32 (95% CI = 1·14-1·52), however, linkage disequilibrium (LD) analysis revealed association of rs2076530 to be secondary to the previously established DRB1 exon 2 encoded position β74 effect although a rare haplotype effect, including both loci, cannot be excluded. Conclusions: BTNL2 may be a sarcoidosis-specific susceptibility loci, although only extensive examination of the whole HLA region in different inflammatory/AIDs will enable DR/DQ independent HLA effects to be determined. © 2006 Blackwell Publishing Ltd.