Genetic association studies of the FOXP3 gene in Graves' disease and autoimmune Addison's disease in the United Kingdom population
Genetic association studies of the FOXP3 gene in Graves' disease and autoimmune Addison's disease in the United Kingdom population
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DOI：
10.1677/jme.1.02072
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发表时间：
2006-08-01
影响因子：
3.5
通讯作者：
Pearce, Simon H. S.
中科院分区：
文献类型：
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作者：
Owen, Catherine J.;Eden, James A.;Pearce, Simon H. S.
调节性T淋巴细胞在调节潜在的自身反应性克隆中起着至关重要的作用，这种细胞类型的功能障碍有助于自身免疫性疾病。FOXP 3是CD 4 + CD 25 +T调节（T-reg）细胞发育和功能的关键决定因素。本研究的目的是调查FOXP 3基因座的遗传多态性是否易患自身免疫性内分泌疾病。我们对633例无关Graves病（GD）受试者、104例自身免疫性Addison病（AAD）受试者和528例健康对照者的高加索队列进行了5个单核苷酸多态性（SNP）和2个微卫星多态性的基因分型。通过限制性内切酶消化或引物延伸-MALDI-TOF（基质辅助激光解吸/电离时间，飞行试验）测定进行SNP基因分型。使用荧光PCR分析微卫星。病例对照分析采用72个等位基因频率列联表。使用UNPHASED软件包进行单倍型分析。与对照组相比，GD或AAD受试者中的7种多态性中的任何一种都没有发现疾病相关的证据（P=0（.）26-0（.）94）。单倍型分析发现一个次要单倍型与GD相关的证据较弱;经多重检验校正后，这一点并不显著。本研究没有发现FOXP 3基因多态性与英国人群GD或AAD易感性相关的有力证据。
Regulatory T lymphocytes play a crucial role in modulating potentially self-reactive clones, and dysfunction of this cell type contributes to autoimmune disease. FOXP3 is a critical determinant of CD4+CD25+T regulatory (T-reg) cell development and function. The aim of this study was to investigate whether genetic polymorphisms at the FOXP3 locus predispose to autoimmune endocrinopathies. Five single nucleotide polymorphisms (SNPs) and two microsatellite polymorphisms were genotyped in our Caucasian cohorts of 633 unrelated Graves' disease (GD) subjects, 104 autoimmune Addison's disease (AAD) subjects and 528 healthy controls. SNP genotyping was performed by either restriction enzyme digestion or by primer-extension-MALDI-TOF (matrix-assisted laser desorption/ionisation time-of, testing flight) assay. Microsatellites were analysed using fluorescent PCR. Case-control analysis was performed using 72 on contingency tables for allele frequency. Haplotype analysis was performed using the UNPHASED package. No evidence for disease association was found with any of the seven polymorphisms in either of the GD or AAD subjects as compared with controls (P=0(.)26-0(.)94). Haplotype analysis found a weak evidence for the association of a minor haplotype with GD; this was not significant when corrected for multiple testing. This study has found no robust evidence that FOXP3 gene polymorphism contributes to the susceptibility to GD or AAD in the UK population.