Bøe Wolff A S, Oftedal B, Johansson S, Bruland O, Løvås K, Meager A, Pedersen C, Husebye E S, Knappskog P M
Institute of Medicine, University of Bergen, Bergen, Norway.
Genes Immun. 2008 Mar;9(2):130-6. doi: 10.1038/sj.gene.6364457. Epub 2008 Jan 17.
Autoimmune Addison's disease (AAD) is often associated with other components in autoimmune polyendocrine syndromes (APS). Whereas APS I is caused by mutations in the AIRE gene, the susceptibility genes for AAD and APS II are unclear. In the present study, we investigated whether polymorphisms or copy number variations in the AIRE gene were associated with AAD and APS II. First, nine SNPs in the AIRE gene were analyzed in 311 patients with AAD and APS II and 521 healthy controls, identifying no associated risk. Second, in a subgroup of 25 of these patients, AIRE sequencing revealed three novel polymorphisms. Finally, the AIRE copy number was determined by duplex quantitative PCR in 14 patients with APS I, 161 patients with AAD and APS II and in 39 healthy subjects. In two Scandinavian APS I patients previously reported to be homozygous for common AIRE mutations, we identified large deletions of the AIRE gene covering at least exon 2 to exon 8. We conclude that polymorphisms in the AIRE gene are not associated with AAD and APS II. We further suggest that DNA analysis of the parents of patients found to be homozygous for mutations in AIRE, always should be performed.
自身免疫性 Addison 病（AAD）常与自身免疫性多内分泌综合征（APS）中的其他成分相关。APS I 由 AIRE 基因突变引起，而 AAD 和 APS II 的易感基因尚不清楚。在本研究中，我们调查了 AIRE 基因的多态性或拷贝数变异是否与 AAD 和 APS II 相关。首先，在 311 例 AAD 和 APS II 患者及 521 例健康对照中分析了 AIRE 基因中的 9 个单核苷酸多态性（SNP），未发现相关风险。其次，在其中 25 例患者的亚组中，AIRE 测序揭示了 3 个新的多态性。最后，通过双重定量 PCR 在 14 例 APS I 患者、161 例 AAD 和 APS II 患者以及 39 例健康受试者中测定了 AIRE 拷贝数。在先前报道为常见 AIRE 突变纯合子的两名斯堪的纳维亚 APS I 患者中，我们发现 AIRE 基因存在大的缺失，至少覆盖外显子 2 至外显子 8。我们得出结论，AIRE 基因的多态性与 AAD 和 APS II 无关。我们进一步建议，对于被发现为 AIRE 基因突变纯合子的患者，应始终对其父母进行 DNA 分析。
