Associations between tumor necrosis factor-alpha and lymphotoxin-alpha polymorphisms and idiopathic recurrent miscarriage

Reproduction. 2008 Mar;135(3):397-403. doi: 10.1530/REP-07-0322.

Abstract

Heightened expression of tumor necrosis factor (TNF)-alpha and lymphotoxin-alpha (LT-alpha) was associated with pregnancy complications, including idiopathic recurrent miscarriage (RM). Whereas TNF-alpha and LT-alpha gene polymorphisms affect serum cytokine concentrations, their contribution to RM is controversial. The single nucleotide polymorphisms (SNPs) TNF-alpha (-238G/A, -308G/A) and LT-alpha (+252A/G) were investigated in 350 RM women and 200 control women. Higher frequency of the TNF-alpha -238A, but not the TNF-alpha -308A or the LT-alpha+252G, allele was seen in patients, with comparable frequencies of TNF-alpha -238G/A, TNF-alpha -308G/A, and LT-alpha+252A/G genotypes seen between both groups, except for TNF-alpha -238G/G, which was lower in patients. Regression analysis confirmed the association of the TNF-alpha -238G/A SNP with idiopathic RM, and both TNF-alpha -308A/TNF -238G/LT-alpha+252G and TNF-alpha -308G/TNF-alpha -238A/LT-alpha+252G haplotypes played a susceptible role in idiopathic RM. TNF-alpha -238G/A and -238A/A, and LT-alpha+252G/G genotypes were positively associated only with exclusively early RM. This supports the concept of the association of TNF-alpha (-238G/A) and LT-alpha (+252A/G) polymorphic variants in idiopathic RM.

MeSH terms

  • Abortion, Habitual / genetics*
  • Abortion, Habitual / immunology*
  • Adult
  • Case-Control Studies
  • Female
  • Gene Expression
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Logistic Models
  • Lymphotoxin-alpha / genetics*
  • Polymorphism, Single Nucleotide*
  • Pregnancy
  • Retrospective Studies
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • Lymphotoxin-alpha
  • Tumor Necrosis Factor-alpha