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

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 c...

Full description

Bibliographic Details
Main Authors: Tan, J., Price, Patricia, Gut, I., Stacey, M., Warrington, N., Wallace, H.
Format: Journal Article
Published: Elsevier Inc. 2010
Online Access:http://hdl.handle.net/20.500.11937/25901
_version_ 1848751834954465280
author Tan, J.
Price, Patricia
Gut, I.
Stacey, M.
Warrington, N.
Wallace, H.
author_facet Tan, J.
Price, Patricia
Gut, I.
Stacey, M.
Warrington, N.
Wallace, H.
author_sort Tan, J.
building Curtin Institutional Repository
collection Online Access
description 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. © 2010 American Society for Histocompatibility and Immunogenetics.
first_indexed 2025-11-14T07:59:02Z
format Journal Article
id curtin-20.500.11937-25901
institution Curtin University Malaysia
institution_category Local University
last_indexed 2025-11-14T07:59:02Z
publishDate 2010
publisher Elsevier Inc.
recordtype eprints
repository_type Digital Repository
spelling curtin-20.500.11937-259012017-09-13T15:25:11Z Characterization of tumor necrosis factor-a block haplotypes associated with susceptibility to chronic venous leg ulcers in Caucasian patients Tan, J. Price, Patricia Gut, I. Stacey, M. Warrington, N. Wallace, H. 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. © 2010 American Society for Histocompatibility and Immunogenetics. 2010 Journal Article http://hdl.handle.net/20.500.11937/25901 10.1016/j.humimm.2010.09.001 Elsevier Inc. restricted
spellingShingle Tan, J.
Price, Patricia
Gut, I.
Stacey, M.
Warrington, N.
Wallace, H.
Characterization of tumor necrosis factor-a block haplotypes associated with susceptibility to chronic venous leg ulcers in Caucasian patients
title Characterization of tumor necrosis factor-a block haplotypes associated with susceptibility to chronic venous leg ulcers in Caucasian patients
title_full Characterization of tumor necrosis factor-a block haplotypes associated with susceptibility to chronic venous leg ulcers in Caucasian patients
title_fullStr Characterization of tumor necrosis factor-a block haplotypes associated with susceptibility to chronic venous leg ulcers in Caucasian patients
title_full_unstemmed Characterization of tumor necrosis factor-a block haplotypes associated with susceptibility to chronic venous leg ulcers in Caucasian patients
title_short Characterization of tumor necrosis factor-a block haplotypes associated with susceptibility to chronic venous leg ulcers in Caucasian patients
title_sort characterization of tumor necrosis factor-a block haplotypes associated with susceptibility to chronic venous leg ulcers in caucasian patients
url http://hdl.handle.net/20.500.11937/25901