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

ABSTRACT

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.

KEYWORDS:

• Mutation
• allele
• real-time PCR
• TLR-2
• TLR-4
• recurrent pregnancy loss

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.