Lack of association between the TGF-β1 gene polymorphisms and recurrent spontaneous abortion

Transforming growth factor-β1 (TGF-β1) is produced by T regulatory lymphocytes (Treg), which play an important role in the physiology of pregnancy. Several polymorphisms of the TGF-β1 gene (TGFB1) have been reported, some with an important correlation with TGF-β1 production and disease severity. We performed an association study between TGFB1 polymorphisms and recurrent spontaneous abortion (RSA). We first used a PCR-RFLP method to detect three known TGFB1 cSNPs (coding single nucleotide polymorphisms) among 111 RSA and 110 normal control women from Southern Iran, such as 29T → C (Leu 10 Pro), 74G → C (Arg 25 Pro) and 788 C → T (Thr 263Ile), and compared their frequencies between the two groups of subjects. To confirm results of the RFLP study and to identify new SNPs in the RSA women, we then sequenced their DNA samples for seven exons and adjacent intronic regions of TGFB1. Consequently, 10 SNPs were detected; one (−14G → A) was located in the upstream region of exon 1, three in exons (two in exon 1 and one in exon 5) and six in intronic regions. Two (IVS5 + 18G → C and IVS6 + 910G → A) of the 10 SNPs were novel. Statistical analysis on the frequency of six most frequent SNPs, including the three cSNPs, as well as on the frequencies of genotypes and 13 haplotypes regarding the 6 SNPs, revealed no significant difference between RSA and control women. Therefore, this study concludes that there is no association between exonic and adjacent intronic polymorphisms of TGFB1 and RSA.