Genetic contribution of tumor necrosis factor (TNF)-alpha gene promoter (-1031, -863 and -857) and TNF receptor 2 gene polymorphisms in endometriosis susceptibility

Am J Reprod Immunol. 2004 May;51(5):352-7. doi: 10.1111/j.1600-0897.2004.00168.x.

Abstract

Problem: Tumor necrosis factor (TNF)-alpha is a major cytokine involved in inflammatory and immune function. The aim of this study was to investigate whether polymorphisms at positions -1031, -863 and -857 in the TNF gene promoter region (TNFA) and TNF receptor type 2 gene (TNFR2) are responsible in part for genetic susceptibility to endometriosis.

Methods of study: TNFA and TNFR2 polymorphisms were determined in 123 patients with endometriosis and 165 fertile healthy women by the polymerase chain reaction (PCR) - preferential homoduplex formation assay and PCR-restriction fragment length polymorphism, respectively.

Results: The frequency of the TNFA-U01 haplotype was increased significantly in patients with endometriosis compared with controls (P = 0.045, OR = 1.45). The TNFA-U01 haplotype was strongly associated with HLA-B*0702. No difference was found in TNFR2 polymorphism between patients and controls.

Conclusion: Our results indicated that TNFA promoter polymorphism was associated with susceptibility to endometriosis. However, this association was not independent of HLA-class I polymorphisms.

MeSH terms

  • Adult
  • Antigens, CD / genetics*
  • Case-Control Studies
  • DNA / genetics
  • DNA / isolation & purification
  • Data Interpretation, Statistical
  • Endometriosis / classification
  • Endometriosis / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • HLA-B Antigens / genetics
  • HLA-B7 Antigen
  • Haplotypes / genetics
  • Heterozygote
  • Homozygote
  • Humans
  • Leukocytes / metabolism
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide / genetics*
  • Promoter Regions, Genetic / genetics
  • Receptors, Tumor Necrosis Factor / genetics*
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • Antigens, CD
  • HLA-B Antigens
  • HLA-B*07:02 antigen
  • HLA-B7 Antigen
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha
  • DNA