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 alpha (TNF-alpha) 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-alpha 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-alpha 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-alpha production and/or mediated responses.
Palmirotta
Raffaele
R
Department of Laboratory Medicine & Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy.
La Farina
Francesca
F
Ferroni
Patrizia
P
Ludovici
Giorgia
G
Nigro
Carmen
C
Savonarola
Annalisa
A
Raparelli
Valeria
V
Riondino
Silvia
S
Rampini
Maria Rita
MR
Guadagni
Fiorella
F
Basili
Stefania
S
D000026:Abortion, Habitual / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D012008:Recurrence; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*; D055815:Young Adult
D014409:Tumor Necrosis Factor-alpha