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A Variant in the BACH2 Gene Is Associated With Susceptibility to Autoimmune Addison's Disease in Humans

Lookup NU author(s): Dr Agnieszka Pazderska, Dr Catherine Napier, Dr Holly FisherORCiD, Professor Heather Cordell, Professor Simon PearceORCiD, Dr Anna MitchellORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Context: Autoimmune Addison's disease (AAD) is a rare but highly heritable condition. The BACH2 protein plays a crucial role in T lymphocyte maturation, and allelic variation in its gene has been associated with a number of autoimmune conditions.Objective: We aimed to determine whether alleles of the rs3757247 single nucleotide polymorphism (SNP) in the BACH2 gene are associated with AAD.Design, Setting, and Patients: This case-control association study was performed in two phases using Taqman chemistry. In the first phase, the rs375 7247 SNP was genotyped in 358 UK AAD subjects and 166 local control subjects. Genotype data were also available from 5154 healthy UK controls from the Wellcome Trust (WTCCC2) for comparison. In the second phase, the SNP was genotyped in a validation cohort comprising 317 Norwegian AAD subjects and 365 controls.Results: The frequency of the minor T allele was significantly higher in subjects with AAD from the United Kingdom compared to both the local and WTCCC2 control cohorts (58% vs 45 and 48%, respectively) (local controls, P = 1.1 x 10(-4); odds ratio [OR], 1.68; 95% confidence interval [CI], 1.29-2.18; WTCCC2 controls, P = 1.4 x 10(-6); OR, 1.44; 95% CI, 1.23-1.69). This finding was replicated in the Norwegian validation cohort (P =.0015; OR, 1.41; 95% CI, 1.14-1.75). Subgroup analysis showed that this association is present in subjects with both isolated AAD (OR, 1.53; 95% CI, 1.22-1.92) and auto immune polyglandular syndrome type 2 (OR, 1.37; 95% CI, 1.12-1.69) in the UK cohort, and with autoimmune polyglandular syndrome type 2 in the Norwegian cohort (OR, 1.58; 95% CI, 1.22-2.06).Conclusion: We have demonstrated, for the first time, that allelic variability at the BACH2 locus is associated with susceptibility to AAD. Given its association with multiple autoimmune conditions, BACH2 can be considered a "universal" autoimmune susceptibility locus.

Publication metadata

Author(s): Pazderska A, Oftedal BE, Napier CM, Ainsworth HF, Husebye ES, Cordell HJ, Pearce SHS, Mitchell AL

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Endocrinology and Metabolism

Year: 2016

Volume: 101

Issue: 11

Pages: 3865-3869

Print publication date: 01/11/2016

Online publication date: 28/09/2016

Acceptance date: 22/09/2016

Date deposited: 16/02/2017

ISSN (print): 0021-972X

ISSN (electronic): 1945-7197

Publisher: Oxford University Press


DOI: 10.1210/jc.2016-2368


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Funder referenceFunder name
Addison's Disease Self-Help Group
Exchange in Endocrinology Expertise program of the European Union of Medical Specialists, Section and Board of Endocrinology
National Institute for Health Research
G0900309Medical Research Council Clinical Research Training Fellowship
MR/J002.526MRC Developmental Clinical Studies