TNFA Gene Promoter Polymorphisms and Susceptibility to Recurrent Pregnancy Loss in Italian Women

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.

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