Association of the BTNL2 rs2076530 single nucleotide polymorphism with Graves' disease appears to be secondary to DRB1 exon 2 position beta74.
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.


METHODS
A case control association study of the rs2076530 polymorphism.


METHODS
Eight hundred sixty-four Graves' disease patients and 864 controls.


METHODS
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 beta74 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.
Simmonds
M J
MJ
Department of Medicine, Division of Medical Sciences, Institute of Biomedical Research, University of Birmingham, Edgbaston, Birmingham, UK.
Heward
J M
JM
Barrett
J C
JC
Franklyn
J A
JA
Gough
S C L
SC
D000071797:Butyrophilins; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005091:Exons; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006111:Graves Disease / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012507:Sarcoidosis / Q000235:genetics; D044465:White People
C408263:BTNL2 protein, human; D000071797:Butyrophilins; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D008562:Membrane Glycoproteins