FoxO1 gene confers genetic predisposition to acute anterior uveitis with ankylosing spondylitis.
FoxO1 gene confers genetic predisposition to acute anterior uveitis with ankylosing spondylitis.
复制标题
FoxO1 基因赋予急性前葡萄膜炎伴强直性脊柱炎的遗传倾向。
DOI：
10.1167/iovs.14-15460
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发表时间：
2014
影响因子：
4.4
通讯作者：
Yang Peizeng
中科院分区：
文献类型：
--
作者：
Yu Hongsong;Liu Yunjia;Zhang Lijun;Wu Lili;Zheng Minming;Cheng Ling;Luo Le;Kijlstra Aize;Yang Peizeng
目的
最近的研究表明，调节性T（Treg）细胞的减少可能有助于急性前葡萄膜炎（AAU）和强直性脊柱炎（AS）的活动。包括IL 2 RA、miR-27 a、miR-182和FoxO 1在内的许多免疫遗传因子与Treg细胞功能相关。在这项研究中，我们调查了这些基因的多态性与AAU与或不与AS在中国汉族人群之间的关联。
方法
采用聚合酶链反应-限制性片段长度多态性（RFLP）分析方法，对680例AAU患者（伴或不伴AS）和1280例对照者进行了两阶段关联研究。通过实时PCR定量基因表达。
结果
在第一阶段研究中，对230例AAU合并AS患者、240例AAU非AS患者和650名对照者进行了10个单核苷酸多态性（SNP）的关联分析。结果显示，FoxO 1/rs 2297626 AA基因型和A等位基因在AAU患者中的频率显著增高（AA基因型：P = 6.23 × 10（-5），OR = 1.86; A等位基因：P = 2.17 × 10（-4），OR = 1.53）。其他9个SNPs与AAU伴或不伴AS无显著关联。在第二阶段的研究中，FoxO 1/rs 2297626在210例AS患者和630名对照中进行关联分析。第二阶段和联合研究证实FoxO 1/rs 2297626与AAU合并AS相关（AA基因型：P = 3.45 × 10（-8），OR = 1.85; A等位基因：P = 1.55 × 10（-7），OR = 1.55）。
结论
这项研究表明，FoxO 1，而不是miR-27 a，miR-182和IL 2 RA，有助于AAU与AS的遗传易感性，但没有测试的多态性赋予风险AAU没有AS。
PURPOSE
Recent studies have shown that a decrease of regulatory T (Treg) cells may contribute to the activity of acute anterior uveitis (AAU) and ankylosing spondylitis (AS). A number of immunogenetic factors including IL2RA, miR-27a, miR-182, and FoxO1 are associated with Treg cell function. In this study, we investigated the association between polymorphisms of these genes and AAU with or without AS in a Chinese Han population.
METHODS
Using PCR-restricted fragment length polymorphism (RFLP) assay, a two-stage association study was performed in 680 AAU patients with or without AS and 1280 controls. Gene expression was quantified by real-time PCR.
RESULTS
In the first stage study, an association analysis of 10 single nucleotide polymorphisms (SNPs) was performed in 230 AAU patients with AS, 240 AAU patients without AS, and 650 controls. The results showed significantly increased frequencies of the FoxO1/rs2297626 AA genotype and A allele in AAU patients with AS (AA genotype: P = 6.23 × 10(-5), odds ratio [OR] = 1.86; A allele: P = 2.17 × 10(-4), OR = 1.53). No significant association of the other 9 SNPs with AAU with or without AS was observed. In the second stage study, an association analysis of FoxO1/rs2297626 was performed in 210 AAU patients with AS and 630 controls. The second stage and combined studies confirmed the association of FoxO1/rs2297626 with AAU with AS (AA genotype: P = 3.45 × 10(-8), OR = 1.85; A allele: P = 1.55 × 10(-7), OR = 1.55).
CONCLUSION
This study suggests that FoxO1, but not miR-27a, miR-182, and IL2RA, contributes to the genetic susceptibility of AAU with AS, but none of the tested polymorphisms confer risk to AAU without AS.