Characterization of tumor necrosis factor–α block haplotypes associated with susceptibility to chronic venous leg ulcers in Caucasian patients

Tan, Joo-Huang; Price, Patricia; Gut, Ivo; Stacey, Michael; Warrington, Nicole M.; Wallace, Hilary

doi:10.1016/j.humimm.2010.09.001

Cited by 10 publications

(9 citation statements)

References 24 publications

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“…Recently several authors postulated that increased levels of pro‐inflammatory cytokines as well as the dysregulation of MMP‐9 and NGAL are involved in impaired healing in patients with chronic venous leg ulcers …”

Section: Discussionmentioning

confidence: 99%

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Chronic venous leg ulcers are associated with high levels of metalloproteinases‐9 and neutrophil gelatinase‐associated lipocalin

Serra

Buffone

Falcone

et al. 2013

Wound Repair Regeneration

112

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Venous ulcers are related to dysfunctions in extracellular matrix. Both matrix metalloproteinases (MMP) and neutrophil gelatinase-associated lipocalin (NGAL) could play a role in the healing process in patients with chronic venous ulcers. We evaluated the role of MMP-9 and NGAL in the healing process in venous ulceration. We performed an open-label, parallel groups, single clinical center study. Patients with chronic venous leg ulcers represented the test group (Group I), whereas patients without chronic ulcers represented the control group (Group II). In Group I plasma and wound fluid samples were collected at the time of admission, at the time of the surgery, and at the follow-up, while ulcer tissues were taken at the time of the surgery. In Group II, plasma and wound fluid were collected at admission and at the time of the surgery, whereas skin tissues were collected at the time of the surgery. Enzyme-linked immunosorbent assay test was used to evaluate the levels of MMP-9 and NGAL in plasma and wound fluid, whereas Western blot analysis was performed to estimate the expression of MMP-9 and NGAL in tissues. Enzyme-linked immunosorbent assay tests revealed significantly higher levels of MMP-9 and NGAL in both plasma and wound fluid of patients with ulcers compared to patients without ulcers (p < 0.01). Moreover, Western blot analysis documented an increased expression of MMP-9 and NGAL in biopsy tissue of patients with ulcers compared to patients without ulcers (p < 0.01). In conclusion MMP-9 and NGAL may correlate with the clinical course of venous ulcers.

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Section: Discussionmentioning

confidence: 99%

“…Chronic wounds, i.e., venous ulcers, exhibit dysfunctions in extracellular matrix that cannot support healing . Some studies reported that both matrix metalloproteinases (MMP) and neutrophil gelatinase‐associated lipocalin (NGAL) could play a role in the healing process in patients with chronic venous ulcers …”

mentioning

confidence: 99%

Chronic venous leg ulcers are associated with high levels of metalloproteinases‐9 and neutrophil gelatinase‐associated lipocalin

Serra

Buffone

Falcone

et al. 2013

Wound Repair Regeneration

112

119

View full text Add to dashboard Cite

show abstract

“…Chronic venous disorders are widespread in western countries and their main complication, that is, venous leg ulcers, with an overall prevalence ranging up to 2% in the general population, is responsible for important socioeconomic problems . Chronic wounds, that is, venous ulcers, exhibit dysfunctions in extracellular matrix that cannot support healing, and some studies reported that both matrix metalloproteinases (MMPs) and neutrophil gelatinase‐associated lipocalin (NGAL) could play a role in the healing process in patients with chronic venous ulcers .…”

Section: Introductionmentioning

confidence: 99%

Doxycycline speeds up healing of chronic venous ulcers

Serra

Gallelli

Buffone

et al. 2013

International Wound Journal

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Venous ulcers are common, with an overall prevalence of up to 2% in the general population of western countries, and have significant socioeconomic impact. Matrix metalloproteinases (MMPs) are involved in the alteration of extracellular matrix that could lead to venous ulceration. Sixty-four patients with venous ulcers were recruited in a 22-month period. All patients were subjected to the most appropriate treatment considering also the patient's wishes (compression therapy followed or not by vein surgery). Patients were randomised into two groups of 32 persons in each (groups A and B). Patients of group A in addition to the basic treatment, described above, received the administration of oral low doses of doxycycline 20 mg b.i.d. for 3 months, whereas patients of group B received basic treatment only. Healing was assessed by means of direct ulcer tracing with computerised planimetry. Group A showed a higher healing rate compared with group B. In group B, the lower healing rate was related to higher levels of MMP-9; neutrophil gelatinase-associated lipocalin and vascular endothelial growth factor, documented in plasma; wound fluid and biopsies executed and compared between both groups. Pharmacological treatments, as doxycycline administration, which by means of its immunomodulatory and anti-inflammatory actions, through the inhibition of MMP, could improve extracellular matrix functioning and represent a possible solution to support wound healing.

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“…Among them, there were the alpha-2 type I collagen gene (COL1A2) [17], matrix metallopeptidase-2 gene (MMP-2) [18], plasminogen activator inhibitor gene (PAI-1) [19], methylene tetrahydrofolate reductase gene (MTHFR C677T mutation) [20], matrix metallopeptidase 9 (MMP-9), and TIMP metallopeptidase inhibitor 2 (TIMP2) genes [21]. Genes examined in association studies performed for chronic venous insufficiency with leg ulcer include fibroblast growth factor receptor 2 gene (FGFR2) [22], the factor V gene (F5, Leiden mutation) [23][24][25][26], tumor necrosis factor-a gene (TNFa) [27], hemochromatosis gene (HFE), solute carrier family 40 gene (SLC40A1), matrix metallopeptidase-12 gene (MMP-12), and coagulation factor XIII gene (FXIII) [28]. Recently, Zamboni et al [29] showed the association of p.282Y (rs1800562 A allele) variant of the hemochromatosis (HFE) gene with the increased risk of venous ulceration.…”

Section: Introductionmentioning

confidence: 99%

HFE p.C282Y gene variant is associated with varicose veins in Russian population

et al. 2015

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Recently, the association of polymorphism rs1800562 (p.C282Y) in the hemochromatosis (HFE) gene with the increased risk of venous ulceration was shown. We hypothesized that HFE gene polymorphism might be involved not only in ulceration process, but also in susceptibility to primary varicose veins. We genotyped HFE p.C282Y (rs1800562) and p.H63D (rs1799945) variants in patients with primary varicose veins (n = 463) and in the control group (n = 754). In our study, p.282Y variant (rs1800562 A allele) was significantly associated with the risk of varicose veins (OR 1.79, 95 % CI = 1.11-2.89, P = 0.02). A borderline significant reverse association of p.63D variant (rs1799945 G allele) with venous leg ulcer development was revealed in Russians (OR 0.25, 95 % CI = 0.06-1.00, P = 0.05), but not in the meta-analysis (P = 0.56). We conclude that the HFE gene polymorphism can affect the risk of developing primary varicose veins.

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Characterization of tumor necrosis factor–α block haplotypes associated with susceptibility to chronic venous leg ulcers in Caucasian patients

Cited by 10 publications

References 24 publications

Chronic venous leg ulcers are associated with high levels of metalloproteinases‐9 and neutrophil gelatinase‐associated lipocalin

Chronic venous leg ulcers are associated with high levels of metalloproteinases‐9 and neutrophil gelatinase‐associated lipocalin

Doxycycline speeds up healing of chronic venous ulcers

HFE p.C282Y gene variant is associated with varicose veins in Russian population

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