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Eur J Endocrinol. 2012 Dec;167(6):825-8. doi: 10.1530/EJE-12-0579. Epub 2012 Sep 25.

The role of functionally defective rare germline variants of sialic acid acetylesterase in autoimmune Addison's disease.

Author information

1
Institute of Genetic Medicine, International Centre for Life, Newcastle University, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK. earn.gan@ncl.ac.uk

Abstract

BACKGROUND:

Autoimmune Addison's disease (AAD) is a rare condition with a complex genetic basis. A panel of rare and functionally defective genetic variants in the sialic acid acetylesterase (SIAE) gene has recently been implicated in several common autoimmune conditions. We performed a case-control study to determine whether these rare variants are associated with a rarer condition, AAD.

METHOD:

We analysed nine SIAE gene variants (W48X, M89V, C196F, C226G, R230W, T312M, Y349C, F404S and R479C) in a United Kingdom cohort of 378 AAD subjects and 387 healthy controls. All samples were genotyped using Sequenom iPlex chemistry to characterise primer extension products.

RESULTS:

A heterozygous rare allele at codon 312 (312*M) was found in one AAD patient (0.13%) but was not detected in the healthy controls. The commoner, functionally recessive variant at codon 89 (89*V) was found to be homozygous in two AAD patients but was only found in the heterozygous state in controls. Taking into account all nine alleles examined, 4/378 (1.06%) AAD patients and 1/387 (0.25%) healthy controls carried the defective SIAE alleles, with a calculated odds ratio of 4.13 (95% CI 0.44-97.45, two-tailed P value 0.212, NS).

CONCLUSION:

We demonstrated the presence of 89*V homozygotes and the 312*M rare allele in the AAD cohort, but overall, our analysis does not support a role for rare variants in SIAE in the pathogenesis of AAD. However, the relatively small collection of AAD patients limits the power to exclude a small effect.

PMID:
23011869
PMCID:
PMC3494867
DOI:
10.1530/EJE-12-0579
[Indexed for MEDLINE]
Free PMC Article
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