TNFA gene promoter polymorphisms and susceptibility to recurrent pregnancy loss in Italian women

Raffaele Palmirotta, Francesca La Farina, Patrizia Ferroni, Giorgia Ludovici, Carmen Nigro, Annalisa Savonarola, Valeria Raparelli, Silvia Riondino, Maria Rita Rampini, Fiorella Guadagni, Stefania Basili

Research output: Contribution to journalArticle


The aim of this study was to investigate the relationship between serum tumor necrosis factor α (TNF-α) levels and single nucleotide polymorphisms (SNPs) of the TNFA gene promoter (-376G/A, -308G/A, and -238G/A) in 100 Italian Caucasian women with reproductive failure and 100 fertile controls. Molecular analysis of TNFA SNPs showed higher frequencies of -238G allele (P =.028) as well as the presence of a 3-loci haplotype (-376G/-308A/-238G; P =.020) in fertile controls compared to women with reproductive failure. Serum TNF-α levels were higher in study women compared to controls ( P =.001). Of interest, the TNFA -376G/-308A/-238G haplotype was an independent predictor of low TNF-α levels (P =.021) and miscarriage (P =.023) in multivariate analyses. In conclusion, these findings support the concept of an association of TNFA polymorphisms and recurrent pregnancy loss (RPL). In particular, the TNFA -238GG variant and the TNFA -376G/-308A/-238G haplotype might represent protective factors, probably through reduced TNF-α production and/or mediated responses.

Original languageEnglish
Pages (from-to)659-666
Number of pages8
JournalReproductive Sciences
Issue number7
Publication statusPublished - Jul 2010



  • Infertility
  • inflammation
  • miscarriage
  • single nucleotide polymorphisms
  • tumor necrosis factor-α

ASJC Scopus subject areas

  • Obstetrics and Gynaecology

Cite this

Palmirotta, R., La Farina, F., Ferroni, P., Ludovici, G., Nigro, C., Savonarola, A., Raparelli, V., Riondino, S., Rampini, M. R., Guadagni, F., & Basili, S. (2010). TNFA gene promoter polymorphisms and susceptibility to recurrent pregnancy loss in Italian women. Reproductive Sciences, 17(7), 659-666.