TLR-4 and VEGF Polymorphisms in Chronic Periaortitis

Abstract

ObjectiveChronic 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.MethodsOne 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).ResultsThere 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]).ConclusionThe 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.

Toll-like receptor-4 signaling pathway in aorta aging and diseases: “its double nature”

“…TLR-4 is recognized to have a key function in the host defence against Gram-negative bacteria, viruses, fungi and mycoplasma [10], but also in the patho-physiology of several age-related diseases [9,11], including CVDs, as stressed in our studies [4,8,11,12] and described by other groups [13][14][15]. Recently, its role has emerged in maintaining aortic homeostasis, but also in establishing aorta aneurysm [4,8,[16][17][18][19][20][21][22][23][24][25][26][27][28][29].…”

“…In fact, the role of TLR-4 mediated receptor signaling pathway in the context of aorta diseases is also emerging [16][17][18][19][20][21][22][23][24][25][26][27][28][29]. In particular, our group postulates its fundamental contribution to the development of sporadic TAA, as reported in the above mentioned model [4,8].…”

Serum vascular endothelial growth factor is associated with cardiovascular involvement and response to therapy in Erdheim-Chester disease

“…Other factors may explain the tissue tropism of ECD. VEGF gene polymorphism has been associated with susceptibility to various types of vasculitis, including giant cell arteritis, Behçet's disease, Kawasaki disease (12) and chronic peri aortitis (13), and further studies will be needed to determine their role in ECD.…”

A functional variant in the 3ˈ-UTR of VEGF predicts the 90-day outcome of ischemic stroke in Chinese patients

“…The VEGFA +936 C > T substitution is an important functional polymorphism that has been proven to alter susceptibility to various diseases that are linked to altered angiogenesis, including, endometriosis [ 30 ], cancer [ 31 , 32 ], and vascular and periaortic diseases [ 33 , 34 ]. A marked heritability of VEGF serum levels according to the +936 C > T genotype has been reported in a healthy Caucasian population [ 35 ].…”