Foxp3 gene polymorphisms and haplotypes associate with susceptibility of Graves' disease in Chinese Han population
Foxp3 gene polymorphisms and haplotypes associate with susceptibility of Graves' disease in Chinese Han population
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Foxp3基因多态性和单倍型与中国汉族人群Graves病易感性的关系
DOI：
10.1016/j.intimp.2015.02.020
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发表时间：
2015-04-01
影响因子：
5.6
通讯作者：
Hu, LiHua
中科院分区：
文献类型：
--
作者：
Zheng, Lei;Wang, XiaoBei;Hu, LiHua
背景：Foxp 3在自身免疫性疾病的发病机制中起重要作用。为探讨Foxp 3基因多态性与中国汉族人群Graves病（GD）易感性的关系，对中国汉族人群Foxp 3基因启动子区-2383、-3279、-3499和内含子区IVS 9 + 459 4个单核苷酸多态性（SNPs）进行基因分型。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对308例GD患者和306例健康对照者进行基因分型。结果：GD患者-3279位点AA/CA基因型和IVS 9 + 459位点CC基因型频率均显著高于正常对照组。GD患者中-3279位点AA/CA基因型女性多于男性。在-3279例GD患者中，TSH水平高或/和TRAb水平低的患者携带A等位基因的频率较高。我们进一步分析了三个SNPs的单倍型，发现单倍型CCA在GD的易感性中起保护作用。相反，CAA和TCA单倍型与GD易感性增加相关。结论：Foxp 3基因启动子功能多态性和单倍型与GD的易感性有关。(C)2015 Elsevier B. V.版权所有。
Background: Foxp3 plays important roles in the pathogenesis of autoimmune diseases. To investigate the association between Foxp3 gene polymorphisms and the susceptibility to Graves' disease (GD) in Chinese Han population, four single nucleotide polymorphisms (SNPs) including -2383, -3279, -3499 in the promoter and IVS9 + 459 in the intron were genotyped.Methods: Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 308 GD patients and 306 healthy controls. The relative expression level of Foxp3 gene was measured by qRT-PCR.Results: The frequencies of AA/CA genotype of-3279 and CC genotype of IVS9 + 459 were significantly higher in GD patients than healthy controls. The AA/CA genotype of -3279 in female GD patients was more frequent than the male. For -3279, GD patients with higher TSH level or/and lower TRAb level were more frequent to carry A allele. We further analyzed the haplotypes of three SNPs and found that the haplotype CCA played a protective role in the susceptibility to GD. In contrast, the CAA and TCA haplotypes were associated with an increased susceptibility to GD. In addition, the mutation from C to A at the position of -3279 reduced the relative luciferase activity of Foxp3 promoter and decreased the expression of Foxp3 in GD patients.Conclusion: Our findings indicated that Foxp3 functional polymorphisms and haplotypes in promoter were associated with the susceptibility to GD in Chinese Han population. (C) 2015 Elsevier B.V. All rights reserved.