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The role of functionally defective rare germline variants of sialic acid acetylesterase in autoimmune Addison's disease
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–co...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioScientifica
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494867/ https://www.ncbi.nlm.nih.gov/pubmed/23011869 http://dx.doi.org/10.1530/EJE-12-0579 |
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author | Gan, Earn H MacArthur, Katie Mitchell, Anna L Pearce, Simon H S |
author_facet | Gan, Earn H MacArthur, Katie Mitchell, Anna L Pearce, Simon H S |
author_sort | Gan, Earn H |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3494867 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioScientifica |
record_format | MEDLINE/PubMed |
spelling | pubmed-34948672012-12-01 The role of functionally defective rare germline variants of sialic acid acetylesterase in autoimmune Addison's disease Gan, Earn H MacArthur, Katie Mitchell, Anna L Pearce, Simon H S Eur J Endocrinol Clinical Study 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. BioScientifica 2012-12 /pmc/articles/PMC3494867/ /pubmed/23011869 http://dx.doi.org/10.1530/EJE-12-0579 Text en © 2012 European Society of Endocrinology http://www.bioscientifica.com/journals/reuselicenceeje/ This is an Open Access article distributed under the terms of the European Journal of Endocrinology's Re-use Licence (http://www.bioscientifica.com/journals/reuselicenceeje/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Clinical Study Gan, Earn H MacArthur, Katie Mitchell, Anna L Pearce, Simon H S The role of functionally defective rare germline variants of sialic acid acetylesterase in autoimmune Addison's disease |
title | The role of functionally defective rare germline variants of sialic acid acetylesterase in autoimmune Addison's disease |
title_full | The role of functionally defective rare germline variants of sialic acid acetylesterase in autoimmune Addison's disease |
title_fullStr | The role of functionally defective rare germline variants of sialic acid acetylesterase in autoimmune Addison's disease |
title_full_unstemmed | The role of functionally defective rare germline variants of sialic acid acetylesterase in autoimmune Addison's disease |
title_short | The role of functionally defective rare germline variants of sialic acid acetylesterase in autoimmune Addison's disease |
title_sort | role of functionally defective rare germline variants of sialic acid acetylesterase in autoimmune addison's disease |
topic | Clinical Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494867/ https://www.ncbi.nlm.nih.gov/pubmed/23011869 http://dx.doi.org/10.1530/EJE-12-0579 |
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