TLR-4 and VEGF Polymorphisms in Chronic Periaortitis

Fabiola Atzeni, Luigi Boiardi, Augusto Vaglio, Davide Nicoli, Enrico Farnetti, Alessandra Palmisano, Nicolò Pipitone, Davide Martorana, Gabriella Moroni, Selena Longhi, Francesco Bonatti, Carlo Buzio, Carlo Salvarani

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Abstract

Objective: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.Methods: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).Results: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]).Conclusion: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.

Original languageEnglish
Article numbere62330
JournalPLoS One
Volume8
Issue number5
DOIs
Publication statusPublished - May 14 2013

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Retroperitoneal Fibrosis
Toll-Like Receptor 4
vascular endothelial growth factors
Polymorphism
Vascular Endothelial Growth Factor A
genetic polymorphism
fibrosis
aneurysm
thrombosis
Abdominal Aortic Aneurysm
homozygosity
alleles
Ureteral Obstruction
vascular endothelial growth factor C
Alleles
cerebrovascular disorders
Venous Thrombosis
Genetic Promoter Regions
myocardial ischemia
aorta

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

TLR-4 and VEGF Polymorphisms in Chronic Periaortitis. / Atzeni, Fabiola; Boiardi, Luigi; Vaglio, Augusto; Nicoli, Davide; Farnetti, Enrico; Palmisano, Alessandra; Pipitone, Nicolò; Martorana, Davide; Moroni, Gabriella; Longhi, Selena; Bonatti, Francesco; Buzio, Carlo; Salvarani, Carlo.

In: PLoS One, Vol. 8, No. 5, e62330, 14.05.2013.

Research output: Contribution to journalArticle

Atzeni, F, Boiardi, L, Vaglio, A, Nicoli, D, Farnetti, E, Palmisano, A, Pipitone, N, Martorana, D, Moroni, G, Longhi, S, Bonatti, F, Buzio, C & Salvarani, C 2013, 'TLR-4 and VEGF Polymorphisms in Chronic Periaortitis', PLoS One, vol. 8, no. 5, e62330. https://doi.org/10.1371/journal.pone.0062330
Atzeni, Fabiola ; Boiardi, Luigi ; Vaglio, Augusto ; Nicoli, Davide ; Farnetti, Enrico ; Palmisano, Alessandra ; Pipitone, Nicolò ; Martorana, Davide ; Moroni, Gabriella ; Longhi, Selena ; Bonatti, Francesco ; Buzio, Carlo ; Salvarani, Carlo. / TLR-4 and VEGF Polymorphisms in Chronic Periaortitis. In: PLoS One. 2013 ; Vol. 8, No. 5.
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abstract = "Objective: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.Methods: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).Results: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]).Conclusion: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.",
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AU - Atzeni, Fabiola

AU - Boiardi, Luigi

AU - Vaglio, Augusto

AU - Nicoli, Davide

AU - Farnetti, Enrico

AU - Palmisano, Alessandra

AU - Pipitone, Nicolò

AU - Martorana, Davide

AU - Moroni, Gabriella

AU - Longhi, Selena

AU - Bonatti, Francesco

AU - Buzio, Carlo

AU - Salvarani, Carlo

PY - 2013/5/14

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N2 - Objective: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.Methods: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).Results: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]).Conclusion: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.

AB - Objective: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.Methods: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).Results: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]).Conclusion: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.

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