Links between SNPs in TLR-2 and TLR-4 and idiopathic recurrent pregnancy loss

Background: Recurrent pregnancy loss is a serious complication of pregnancy and failure of the innate immune system, one part of which are toll-like receptors (TLRs). We hypothesised links between variants of TLR-2 and TLR-4 with recurrent pregnancy loss.Subjects and methods: We recruited 335 women with recurrent pregnancy loss, defined as ≥3 consecutive spontaneous miscarriage of unknown aetiology, and 331 age-matched control women. TLR-2 rs1898830 and rs4696483 and TLR-4 rs2770150, rs1554973 and rs7856729 genotyping were performed by allelic exclusion method (real-time PCR).Result: Of the five tested TLR-2 and TLR-4 tag-SNPs, minor allele frequency of TLR-2 rs1898830 was significantly more frequent in recurrent pregnancy loss patients than in controls. Significantly higher frequencies of homozygous (2/2) TLR-2 rs1898830 (14.1% vs. 8.9%) genotype carriers were seen between recurrent pregnancy loss cases and control women. Haploview analysis identified 1-locus TLR-2 haplotype (GC) that was positively associated with recurrent pregnancy loss. No TLR-4 haplotypes associated with altered recurrent pregnancy loss risk were identified.Conclusion: These findings confirm positive associations of TLR-2 rs1898830 with recurrent pregnancy loss, further supporting a role for TLR signalling in defining pregnancy outcome.