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 C., Warrington, Nicole M. and Wallace, Hilary J. (2010) Characterization of tumor necrosis factor-α block haplotypes associated with susceptibility to chronic venous leg ulcers in Caucasian patients. Human Immunology, 71 12: 1214-1219. doi:10.1016/j.humimm.2010.09.001


Author Tan, Joo-Huang
Price, Patricia
Gut, Ivo
Stacey, Michael C.
Warrington, Nicole M.
Wallace, Hilary J.
Title Characterization of tumor necrosis factor-α block haplotypes associated with susceptibility to chronic venous leg ulcers in Caucasian patients
Journal name Human Immunology   Check publisher's open access policy
ISSN 0198-8859
1879-1166
Publication date 2010
Year available 2010
Sub-type Article (original research)
DOI 10.1016/j.humimm.2010.09.001
Open Access Status
Volume 71
Issue 12
Start page 1214
End page 1219
Total pages 6
Place of publication Philadelphia, PA United States
Publisher Elsevier Inc.
Collection year 2011
Language eng
Subject 2403 Immunology
2723 Immunology and Allergy
Abstract Polymorphisms in the central major histocompatibility complex (MHC) are associated with several immunopathologic and inflammatory diseases, including chronic venous leg ulcers (CVLU). Because of strong linkage disequilibrium, identification of loci affecting disease susceptibility must be based on comparisons between haplotypes. Here we examine the association of conserved tumor necrosis factor (TNF) block haplotypes with CVLU susceptibility. A total of 171 Caucasian patients with CVLU were compared with 173 age-/gender-matched controls, excluding individuals with type 1 diabetes or rheumatoid arthritis. A total of 194 healthy subjects formed a separate population-based control group. Samples were typed for 38 tumor necrosis factor (TNF) block single nucleotide polymorphisms (SNP), human leukocyte antigen (HLA)-B and HLA-DRB1 alleles. TNF haplotypes were derived using the PHASE algorithm and assigned numbers (FVx) defined previously. The patients and matched controls shared 16 TNF block haplotypes. The patients had increased carriage of FV16 and alleles of the 8.1 and 60.3 MHC ancestral haplotypes (AH). CVLU risk is modulated by alleles within FV16 (e.g., TNF-308A and BAT1intron10 C insertion) or near FV16 in the 8.1AH. CVLU risk may also be mediated by unidentified alleles (not in FV22) marked by HLA-B40 and HLA-DR13. FV16 appears to be the best MHC and TNF block marker of susceptibility. After disease onset, an individual's TNF block haplotype does not modulate CVLU severity.
Keyword Chronic venous leg ulcers
Genetic susceptibility
Haplotype
Major histocompatibility complex
Tumor necrosis factor
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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