Tumor Necrosis Factor Alpha Gene Polymorphism Associated with Increased Susceptibility to Venous Leg Ulceration

Wallace, Hilary; Vandongen, Y.K.; Stacey, Michael

doi:10.1038/sj.jid.5700143

Cited by 36 publications

(41 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…TNFA-308*2 and TNFA-1031*2 lie in distinct "TNF block haplotypes". A common disease associated haplotype incorporating TNFA-308 (rs1800629) is marked by a SNP in the BAT1 gene and is associated with venous leg ulcers and sepsis in Caucasians [17,18]. TNF-308*2 was not found in a small cohort of Australian HIV patients with IRD associated with non-tuberculous mycobacteria, but was present in 24-34% of controls (p = 0.015 − 0.035) [9].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Search for a Genetic Factor Associating with Immune Restoration Disease in HIV Patients Co-Infected withMycobacterium tuberculosis

et al. 2013

View full text Add to dashboard Cite

Abstract. BACKGROUND: Up to 43% of HIV-infected patients co-infected with Mycobacterium tuberculosis experience exacerbations of tuberculosis (TB) after commencing antiretroviral therapy (ART). These are termed immune restoration disease (IRD). It is unclear why individual susceptibility varies. OBJECTIVE: We investigate if single nucleotide polymorphisms (SNP) in genes encoding cytokines, chemokines and their receptors associate with development of an IRD event in patients of two different ethnicities. METHODS: DNA samples were available from small well-characterised groups of HIV patients treated in Cambodia (TB-IRD, n = 17; HIV + TB + controls, n = 55) and India (TB-IRD, n = 19; HIV + TB + controls, n = 43). HIV patients with a TB diagnosis but no evidence of IRD were included to control for susceptibility to TB per se. Sixteen SNP implicated in inflammation or mycobacterial disease were genotyped. RESULTS: Susceptibility to TB-IRD associated with carriage of TNFA-1031*T (rs1799964; P = 0.05) and SLC11A1 D543N*G (rs17235409; P = 0.04) in Cambodian patients and carriage of IL18-607*G (rs1946518; P = 0.02) and VDR FokI (F/f)*T (rs10735810; P = 0.05) in Indian patients. CONCLUSIONS: Associations between polymorphisms in immune-related genes and TB-IRD were found, but none were common across two ethnicities.

show abstract

Section: Discussionmentioning

confidence: 99%

“…BAT1 intron 10 (rs9281523) was genotyped using a custom TaqMan assay [17]. DNA samples were diluted to 10 ng/µL and amplified on an ABI Prism 7900 HT (Applied Biosystems) or Roche LC480 (Roche Applied Science, Indianapolis, IL, USA) in 384-well microtiter plates.…”

Section: Hivmentioning

confidence: 99%

The Search for a Genetic Factor Associating with Immune Restoration Disease in HIV Patients Co-Infected withMycobacterium tuberculosis

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Levels of TNF-a and interleukin-1 (IL-1) are higher in venous leg ulcers compared with normal acute wounds, with certain SNPs (such as the 2308A variant in TNF-a) conferring a higher risk of venous ulceration compared with wild-type. 5,22,28 Along with demonstrating the previously mentioned association with TNF-a, Wallace et al 28 also identified a polymorphism in intron 10 of the BAT1 gene (human leukocyte antigen B-associated transcript-1) as being a significant risk factor for venous ulceration.…”

Section: Venous Ulcerationmentioning

confidence: 99%

Genetic polymorphisms of vein wall remodeling in chronic venous disease: a narrative and systematic review

Bharath

Kahn

Lazo‐Langner

2014

Blood

View full text Add to dashboard Cite

Chronic venous disease encompasses a spectrum of disorders caused by an abnormal venous system. They include chronic venous insufficiency, varicose veins, lipodermatosclerosis, postthrombotic syndrome, and venous ulceration. Some evidence suggests a genetic predisposition to chronic venous disease from gene polymorphisms associated mainly with vein wall remodeling. The literature exploring these polymorphisms has not been reviewed and compiled thus far. In this narrative and systematic review, we present the current evidence available on the role of polymorphisms in genes involved in vein wall remodeling and other pathways as contributors to chronic venous disease. We searched the EMBASE, Medline, and PubMed databases from inception to 2013 for basic science or clinical studies relating to genetic associations in chronic venous disease and obtained 38 relevant studies for this review. Important candidate genes/proteins include the matrix metalloproteinases (extracellular matrix degradation), vascular endothelial growth factors (angiogenesis and vessel wall integrity), FOXC2 (vascular development), hemochromatosis (involved in venous ulceration and iron absorption), and various types of collagen (contributors to vein wall strength). The data on associations between these genes/proteins and the postthrombotic syndrome are limited and additional studies are required. These associations might have future prognostic and therapeutic implications.

show abstract

“…Venous leg ulcer (VLU) is multifactorial disease with wellknown acquired and putative inherited predisposing factors [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. Besides the characteristic acquired etiological factors, such as venous insufficiency, obesity, and deep vein thrombosis, case-control studies suggest putative inherited etiological factors, which may also contribute to the mechanism of delayed or pathological wound healing and hence to the development of leg ulcer.…”

Section: Introductionmentioning

confidence: 99%

Chronic Nonhealing Wounds: Could Leg Ulcers Be Hereditary?

Nagy

Szabad

Szolnoky

et al. 2013

Ulcers

View full text Add to dashboard Cite

Background. A number of well-known acquired and putative inherited etiological factors contribute to the development of venous leg ulcer (VLU). Aim. In this study we set out to perform a meta-analysis of putative genetic and acquired factors predisposing to VLU development. Methods. VLU patients ( = 157) were divided into three subgroups in accordance with their acquired etiological factors. The frequencies of four genetic factors were determined: the R506Q (Leiden) mutation of the F5 gene, the G20210A mutation of the F2 (prothrombin) gene, the 2451 A/G SNP of the fibroblast growth factor receptor 2 (FGFR2) 3 UTR, and the −308 G/A SNP of the tumor necrosis factor (TNFA) promoter. Results. The −308 TNFA SNP exhibited a higher frequency among VLU patients without known acquired predisposing factor in their history, than among patients with thrombosis or soft tissue infection in their history (Fisher = 0.0173). Conclusions. This study has demonstrated that the group of VLU patients is heterogeneous in their genetic predisposing factors. Further large-scale studies are needed to delineate the associations among genetic and acquired etiological factors with regard to VLU development and to integrate the consequences of the already known genetic factors to the management of VLU.

show abstract

Tumor Necrosis Factor Alpha Gene Polymorphism Associated with Increased Susceptibility to Venous Leg Ulceration

Cited by 36 publications

References 20 publications

The Search for a Genetic Factor Associating with Immune Restoration Disease in HIV Patients Co-Infected withMycobacterium tuberculosis

The Search for a Genetic Factor Associating with Immune Restoration Disease in HIV Patients Co-Infected withMycobacterium tuberculosis

Genetic polymorphisms of vein wall remodeling in chronic venous disease: a narrative and systematic review

Chronic Nonhealing Wounds: Could Leg Ulcers Be Hereditary?

Contact Info

Product

Resources

About