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.
- single nucleotide polymorphisms
- tumor necrosis factor-α
ASJC Scopus subject areas
- Obstetrics and Gynaecology