汉族银屑病患者 FOXP3 基因多态性。

Polymorphisms in the FOXP3 gene in Han Chinese psoriasis patients.

机构信息

Department of Dermatology of Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.

出版信息

J Dermatol Sci. 2010 Jan;57(1):51-6. doi: 10.1016/j.jdermsci.2009.09.010. Epub 2009 Nov 2.

DOI:10.1016/j.jdermsci.2009.09.010

PMID:19880293

Abstract

BACKGROUND

Psoriasis is a common dermatological disorder, in which autoimmunity plays an important role. CD4(+)CD25(+) regulatory T cells (T-regs) have been suggested to be involved in the pathogenesis of some autoimmune diseases. T-regs express the fork head/winged helix transcription factor, FOXP3, which appears to be of key importance in the development and function of T-regs. Studies have found that single-nucleotide polymorphisms (SNPs) in the FOXP3 gene contribute to susceptibility to some autoimmune disorders. However, information about FOXP3 gene in psoriasis is limited.

OBJECTIVE

This study evaluated the association between FOXP3 gene SNPs and susceptibility to psoriasis in a Han Chinese population.

METHODS

In a hospital-based case-control study, 524 patients with psoriasis and 549 psoriasis-free controls were recruited according to age and gender. We investigated four SNPs in the FOXP3 gene (-6054, deletion/ATT; -3279, A/C; -924, A/G; IVS9+459, A/G) in psoriatic patients, and assessed allele and genotype frequencies in psoriatic patients (237 females, 287 males) and normal controls (272 females, 277 males). The polymorphisms were genotyped using the PCR sequence-specific primer (PCR-SSP) technique and PCR-restriction fragment length polymorphism (RFLP) analysis.

RESULTS

We found that increased risk of psoriasis was associated with the FOXP3 -3279 AC genotype (adjusted OR, 1.32; 95% CI, 1.01-1.74) and the combined AC+AA genotype (adjusted OR, 1.38; 95% CI, 1.07-1.78), compared with the -3279 CC genotype. We also found that an increased risk of psoriasis was associated with the FOXP3 IVS9+459 GG genotype (adjusted OR, 2.24; 95% CI, 1.41-3.58). However, the combined GA+GG genotype showed no such tendency (adjusted OR=1.28; 95% CI, 1.00-1.64), compared with the IVS9+459 AA genotype. There was no evidence of an increased risk associated with the FOXP3-6054 deletion/ATT or FOXP3-924 A/G genotype. In combined genotype analyses, the FOXP3-3279 AC+AA genotype was more obviously associated in males (adjusted OR=1.60, 95% CI=1.11-2.31) and severe psoriasis patients (PASI score >20; adjusted OR=1.97, 95% CI=1.41-2.75). Meanwhile, the FOXP3 IVS9+459 GA+GG genotype was also associated with severe psoriasis patients (adjusted OR=1.69, 95% CI=1.21-2.36).

CONCLUSIONS

FOXP3 polymorphisms appear to contribute to the risk of psoriasis in a Han Chinese population. Larger studies are needed to confirm these findings.

摘要

背景

银屑病是一种常见的皮肤科疾病，其发病机制中存在自身免疫反应。调节性 T 细胞（T-regs）表达叉头/翅膀状螺旋转录因子 FOXP3，其可能在 T-regs 的发育和功能中起关键作用。研究发现，FOXP3 基因的单核苷酸多态性（SNPs）与某些自身免疫性疾病的易感性有关。然而，有关银屑病中 FOXP3 基因的信息有限。

目的

本研究旨在评估汉族人群中 FOXP3 基因 SNP 与银屑病易感性的关系。

方法

采用基于医院的病例对照研究，根据年龄和性别招募了 524 例银屑病患者和 549 例非银屑病对照者。我们在银屑病患者（237 名女性，287 名男性）和正常对照者（272 名女性，277 名男性）中调查了 FOXP3 基因中的四个 SNP（-6054、缺失/ATT；-3279、A/C；-924、A/G；IVS9+459、A/G），并评估了等位基因和基因型频率。采用聚合酶链反应序列特异性引物（PCR-SSP）技术和 PCR 限制性片段长度多态性（RFLP）分析进行基因分型。

结果

我们发现 FOXP3-3279 AC 基因型（调整后的 OR，1.32；95%CI，1.01-1.74）和 AC+AA 基因型（调整后的 OR，1.38；95%CI，1.07-1.78）与银屑病风险增加相关，与-3279 CC 基因型相比。我们还发现 FOXP3 IVS9+459 GG 基因型（调整后的 OR，2.24；95%CI，1.41-3.58）与银屑病风险增加相关。然而，与 IVS9+459 AA 基因型相比，FOXP3 IVS9+459 GA+GG 基因型没有表现出这种趋势（调整后的 OR=1.28；95%CI，1.00-1.64）。FOXP3-6054 缺失/ATT 或 FOXP3-924 A/G 基因型与银屑病风险增加无关。在合并基因型分析中，FOXP3-3279 AC+AA 基因型在男性（调整后的 OR=1.60，95%CI=1.11-2.31）和严重银屑病患者（PASI 评分>20；调整后的 OR=1.97，95%CI=1.41-2.75）中与银屑病风险增加更为明显相关。同时，FOXP3 IVS9+459 GA+GG 基因型也与严重银屑病患者相关（调整后的 OR=1.69，95%CI=1.21-2.36）。