微小RNA-182的基因变异与白塞病和VKH综合征的易感性
Predisposition to Behçet's disease and VKH syndrome by genetic variants of miR-182.
作者信息
Yu Hongsong, Liu Yunjia, Bai Lin, Kijlstra Aize, Yang Peizeng
机构信息
The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, 400016, People's Republic of China.
出版信息
J Mol Med (Berl). 2014 Sep;92(9):961-7. doi: 10.1007/s00109-014-1159-9. Epub 2014 May 8.
UNLABELLED
Previous studies have identified miR-182, miR-27a, FoxO1, and IL2RA as regulatory factors for Treg cell development and function. In order to investigate the association of miR-182, miR-27a, FoxO1, and IL2RA gene polymorphisms with Behçet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population, a two-stage association study was performed in 820 BD, 900 VKH patients, and 1,800 controls using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. In the first stage study, association analysis of 10 single nucleotide polymorphisms (SNPs) was performed in 400 BD, 400 VKH patients, and 600 controls. The results showed significantly decreased frequencies of the miR-182/rs76481776 CC genotype and C allele in BD (P = 3.36 × 10(-4), OR = 0.55; P = 4.74 × 10(-4), OR = 0.59) and VKH patients (P = 1.11 × 10(-4), OR = 0.53; P = 1.26 × 10(-4), OR = 0.56). No significant association of the other nine SNPs with BD or VKH was observed. In the second stage study, association analysis of miR-182/rs76481776 was performed in 420 BD, 500 VKH patients, and 1,200 controls. The second stage and combined studies confirmed the association of miR-182/rs76481776 with BD (CC genotype: P = 3.25 × 10(-7), OR = 0.58; C allele: P = 1.81 × 10(-7), OR = 0.60) and VKH (CC genotype: P = 7.89 × 10(-8), OR = 0.57; C allele: P = 2.52 × 10(-8), OR = 0.59). Real-time PCR analysis showed a significantly increased expression of miR-182 in TT/CT cases compared to CC cases in anti-CD3/CD28 antibodies-stimulated CD4(+) T cells (P = 2.1 × 10(-2)). In conclusion, this study suggests that miR-182, but not miR-27a, FoxO1, and IL2RA, contributes to the genetic susceptibility of BD and VKH.
KEY MESSAGE
MiR-182 contributes to genetic susceptibility of BD and VKH. No significant association of miR-27a, FoxO1, and IL2RA with BD or VKH was observed. Significantly increased expression of miR-182 in TT/CT cases compared to CC cases was observed.
未标注
先前的研究已确定miR-182、miR-27a、FoxO1和IL2RA是调节性T细胞（Treg）发育和功能的调控因子。为了研究miR-182、miR-27a、FoxO1和IL2RA基因多态性与中国汉族人群中白塞病（BD）和葡萄膜炎-小柳原田综合征（VKH）的关联，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析方法，对820例BD患者、900例VKH患者和1800例对照进行了两阶段关联研究。在第一阶段研究中，对400例BD患者、400例VKH患者和600例对照进行了10个单核苷酸多态性（SNP）的关联分析。结果显示，BD患者（P = 3.36×10⁻⁴，OR = 0.55；P = 4.74×10⁻⁴，OR = 0.59）和VKH患者（P = 1.11×10⁻⁴，OR = 0.53；P = 1.26×10⁻⁴，OR = 0.56）中miR-182/rs76481七七六CC基因型和C等位基因的频率显著降低。未观察到其他9个SNP与BD或VKH有显著关联。在第二阶段研究中，对420例BD患者、500例VKH患者和1200例对照进行了miR-182/rs76481七七六的关联分析。第二阶段及合并研究证实了miR-182/rs76481七七六与BD（CC基因型：P = 3.25×10⁻⁷，OR = 0.58；C等位基因：P = 1.81×10⁻⁷，OR = 0.60）和VKH（CC基因型：P = 7.89×10⁻⁸，OR = 0.57；C等位基因：P = 2.52×10⁻⁸）的关联。实时PCR分析显示，在抗CD3/CD28抗体刺激的CD4⁺T细胞中，与CC病例相比，TT/CT病例中miR-182的表达显著增加（P = 2.1×10⁻²）。总之，本研究表明，miR-十八二，而非miR-27a、FoxO1和IL2RA，与BD和VKH的遗传易感性有关。
关键信息
MiR-182与BD和VKH的遗传易感性有关；未观察到miR-27a、FoxO1和IL2RA与BD或VKH有显著关联；观察到与CC病例相比，TT/CT病例中miR-182的表达显著增加。
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