W Bahia1, I Soltani2, A Haddad3, A Radhouani4, Abdelkarim Mahdhi5, S Ferchichi1, W Y Almawi6,7. 1. Research Unit of Clinical and Molecular Biology, Faculty of pharmacy, University of Monastir, Monastir, Tunisia. 2. Molecular and Cellular Hematology Laboratory, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia. 3. Department Obstetrics and Gynecology, Fattouma Bourguiba University Hospital, Monastir, Tunisia. 4. Faculty of Medicine, University of Tunis El Manar, Tunis, Tunisia. 5. Laboratory of Analysis, Treatment and Valorization of Pollutants of the Environment and Products, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia. 6. Faculty of Sciences, El Manar University, Tunis, Tunisia. 7. School of Medicine, Nazarbayev University, Astana, Kazakhstan.
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.
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-2rs1898830 and rs4696483 and TLR-4rs2770150, 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-2rs1898830 was significantly more frequent in recurrent pregnancy loss patients than in controls. Significantly higher frequencies of homozygous (2/2) TLR-2rs1898830 (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-2rs1898830 with recurrent pregnancy loss, further supporting a role for TLR signalling in defining pregnancy outcome.
Entities:
Keywords:
Mutation; TLR-2; TLR-4; allele; real-time PCR; recurrent pregnancy loss