Rheumatology Unit, L. Sacco University Hospital of Milan, Milan, Italy.
PLoS One. 2013 May 14;8(5):e62330. doi: 10.1371/journal.pone.0062330. Print 2013.
Chronic periaortitis (CP) is a rare disease that is characterised by fibro-inflammatory tissue surrounding the abdominal aorta and has both non-aneurysmal (idiopathic retroperitoneal fibrosis [IRF]) and aneurysmal forms (inflammatory abdominal aortic aneurysm [IAAA]). We investigated whether toll-like receptor 4 (TLR-4) and vascular endothelial growth factor (VEGF) polymorphisms were associated with susceptibility to, and the clinical features of CP.
One hundred and two CP patients and 200 healthy controls were molecularly genotyped for TLR-4 gene polymorphism (+896 A/G) (rs4986790), VEGF mutations +936 C/T (rs3025039) and -634 C/G (rs2010963), and an 18 base pair (bp) insertion/deletion (I/D) polymorphism at -2549 of the VEGF promoter region. The patients were grouped on the basis of the type of CP (IRF or IAAA), and the presence or absence of established atherosclerotic disease (ischemic heart disease, cerebrovascular disease, and peripheral arterial disease).
There were no significant differences in the distribution of the studied polymorphisms between the patients and controls. However, carriage of the +936 T allele was significantly more frequent in the patients with IRF than in those with IAAA (26.5% vs 5.3%; p = 0.046; OR 6.49 [95% CI 0.82-51.54]). There were significantly more carriers of the I allele among the patients with ureteral obstruction (83.8% vs 58.8%; p = 0.006; OR 3.63 [95% CI 1.42-9.28]) and those who received conservative treatment (48.5% vs 23.5%; p = 0.015; OR 3.06 [95% CI 1.22-7.721]) than among those without, and II homozygosity was significantly more frequent in the patients with deep vein thrombosis than in those without (30.4% vs 11.7%, p = 0.031; OR 3.31 [95% CI 1.07-10.21]).
The VEGF +936 C/T polymorphism may be associated with an increased risk of developing the non-aneurysmal IRF form of CP. Carriers of the I allele and II homozygosity are respectively at increased risk of developing ureteral obstruction and deep vein thrombosis.
慢性大动脉炎（CP）是一种罕见疾病，其特征为纤维炎症组织围绕腹主动脉，具有非动脉瘤（特发性腹膜后纤维化[IRF]）和动脉瘤（炎症性腹主动脉瘤[IAAA]）两种形式。我们研究了 Toll 样受体 4（TLR-4）和血管内皮生长因子（VEGF）多态性是否与 CP 的易感性和临床特征相关。
对 102 名 CP 患者和 200 名健康对照者进行 TLR-4 基因多态性（+896A/G）（rs4986790）、VEGF 突变+936C/T（rs3025039）和-634C/G（rs2010963）以及 VEGF 启动子区-2549 位 18 个碱基（bp）插入/缺失（I/D）多态性的分子基因分型。根据 CP 类型（IRF 或 IAAA）以及是否存在已确立的动脉粥样硬化疾病（缺血性心脏病、脑血管病和外周动脉疾病）对患者进行分组。
患者与对照组之间研究多态性的分布无显著差异。然而，IRF 患者中+936T 等位基因的携带率明显高于 IAAA 患者（26.5%比 5.3%；p=0.046；OR 6.49[95%CI 0.82-51.54]）。与无输尿管梗阻的患者相比，患有输尿管梗阻的患者携带 I 等位基因的比例显著更高（83.8%比 58.8%；p=0.006；OR 3.63[95%CI 1.42-9.28]），且接受保守治疗的患者（48.5%比 23.5%；p=0.015；OR 3.06[95%CI 1.22-7.721]）也高于无输尿管梗阻的患者，且 II 纯合子在患有深静脉血栓的患者中比在无深静脉血栓的患者中更常见（30.4%比 11.7%，p=0.031；OR 3.31[95%CI 1.07-10.21]）。
VEGF+936C/T 多态性可能与非动脉瘤性 IRF 型 CP 的发病风险增加有关。携带 I 等位基因和 II 纯合子的患者分别具有发生输尿管梗阻和深静脉血栓的风险增加。
