SFEBES2016 Oral Communications Adrenal and Steroids (6 abstracts)
A Single Nucleotide Polymorphism in the BACH2 Gene Contributes to Susceptibility to Autoimmune Addison’s Disease in UK and Norwegian cohorts
Agnieszka Pazderska 1 , Bergithe Oftedal 2 , Catherine Napier 1 , Holly Ainsworth 1 , Eystein Husebye 2, , Heather Cordell 1 , Simon Pearce 1 & Anna Mitchell 1
1Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK; 2Department of Clinical Science, University of Bergen, 5021 Bergen, Norway; 3Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway.
Background: Autoimmune Addison disease (AAD) is a rare but highly heritable endocrinopathy. The BACH2 protein plays a crucial role in T lymphocyte maturation, and in particular in regulatory T cell formation, and allelic variation in its gene has been associated with autoimmune conditions such as type 1 diabetes, autoimmune thyroid disease and vitiligo. Its role in susceptibility to autoimmune Addison’s disease (AAD) has not been investigated.
Aim: To investigate whether the intronic SNP rs3757247 in the BACH2 gene is associated with AAD.
Methodology: A case-control association study was performed. The rs3757247 SNP was genotyped in 357 UK AAD patients using Taqman chemistry (Life Technologies) and results compared to genotype data from 5097 healthy individuals available from the Wellcome Trust (WTCCC2). The SNP was then genotyped in a validation cohort comprising of 330 Norwegian AAD subjects and 384 local controls. Statistical association analysis was performed using PLINK.
Results: The minor T allele frequency was significantly higher in UK AAD subjects compared to the controls (58% vs 48%; p=1.4×10−6; OR 1.44 [95% CI 1.23–1.69]). This finding was replicated in the Norwegian validation cohort (p=0.0015; OR 1.41 [95% CI 1.14–1.75]). Subgroup analysis showed that this association is true for both isolated AAD (iAAD; OR 1.53 [95% CI 1.22–1.92]) and autoimmune polyglandular syndrome type 2 (APS2; OR 1.37 [95% CI 1.12–1.69]) in the UK cohort, and for APS2 in the Norwegian cohort (OR 1.58 [95% CI 1.22–2.06].
Interpretation and conclusion: This is the first report of a BACH2 variant being associated with susceptibility to AAD. The association of BACH2 SNPs with multiple autoimmune endocrinopathies supports existing evidence that the BACH2 protein is a crucial regulator of immune function and dysfunction.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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