Linkage disequilibrium between TNF-α-308 G/A promoter and histocompatibility leukocyte antigen alleles in Han-nationality lung transplant recipients from Eastern China

Exp Clin Transplant. 2013 Jun;11(3):264-9. doi: 10.6002/ect.2012.0099. Epub 2012 Nov 19.

Abstract

Objectives: Genes encoding histocompatibility leukocyte antigen (HLA) and proinflammatory cytokines are involved in rejection after organ transplant. The authors explored the association between HLA alleles and the tumor necrosis factor (TNF)- α-308 G/A promoter region in lung transplant recipients of Han nationality from East China. They also evaluated the correlation between TNF-α-308 G/A and the onset of acute rejection after lung transplant.

Materials and methods: All lung transplant recipients of Han nationality who were admitted into our hospital between August 2004 and July 2011 were included. Patients were divided into 2 groups according to the presence or absence of acute rejection episodes. Genotypes of HLA and single nucleotide polymorphisms of TNF-α-308 G/A were determined using polymerase chain reaction-single specific primer kits.

Results: A total of 106 lung transplant recipients were investigated. HLA-A*2 allele was in linkage disequilibrium with TNF-α-308 G allele. HLA-A*33, -B*58 and -DRB1*03 alleles were in linkage disequilibrium with TNF-α-308 A allele. Notably, TNF-α-308 A allele was in complete linkage disequilibrium with HLA-B*58 allele. Furthermore, TNF-α-308 A allele was in linkage disequilibrium with the HLA-A*33-DRB1*03 and HLA-B*58-DRB1*03 haplotypes. Clinical analysis indicated that TNF-α-308 G/A was not associated with onset of acute rejection after lung transplant.

Conclusions: TNF-α-308 G/A polymorphism was strongly associated with HLA-A*2, -A*33, -B*58, and -DRB1*03 alleles in our population. HLA genotyping can identify lung transplant recipients carrying the highly productive phenotype of TNF-α-308 A allele, which may provide information on rejection after transplant. However, the authors found that TNF-α-308 A subtype has no correlation with acute rejection after lung transplant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Asian People / genetics*
  • Chi-Square Distribution
  • China / epidemiology
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Graft Rejection / ethnology
  • Graft Rejection / genetics*
  • Graft Rejection / immunology
  • HLA Antigens / genetics*
  • HLA-A Antigens / genetics
  • HLA-B Antigens / genetics
  • HLA-DRB1 Chains / genetics
  • Humans
  • Linkage Disequilibrium*
  • Lung Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic*
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Tumor Necrosis Factor-alpha / genetics*
  • Young Adult

Substances

  • HLA Antigens
  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-DRB1 Chains
  • Tumor Necrosis Factor-alpha