Haplotype-based association of two SNPs in miR-423 with unexplained recurrent pregnancy loss in a Chinese Han population.

MicroRNAs (miRNAs) regulate diverse cellular processes such as cell differentiation, proliferation and apoptosis. Mutation in miRNAs results in various pathological conditions such as inflammation, viral infections, neurodegeneration, and autoimmunity. We have evaluated the association of miR-423 rs6505162C>A and rs8067576 A>T among patients with recurrent pregnancy loss (RPL) and controls from North China. Our study found that one SNP rs6505162C>A in miR-423 coding region was associated with the increase risk of humanunexplained RPL (URPL), but no differences were found in another SNP rs8067576 A>T. However, in two-locus haplotype analysis, miR-423-CC/TT haplotype was associated with an increased risk of URPL. The level of mature miR-423 was obviously down-regulated in cells transfected with miR-423-CC/TT haplotype. miR-423-CC/TT haplotype inhibited HTR-8/SVneo cells proliferation and migration and promoted cells apoptosis. Further experiments identified that mesoderm development candidate 1 (MESDC1) was a functionally relevant target of miR-423, and its expression was reversely regulated by miR-423. More importantly, dual-luciferase assay indicated miR-423-CC/TT haplotype decreasing miR-423 expression, could up-regulate MESDC1 expression. Collectively, our data suggest that miR-423-CC/TT haplotype in pre-miR-423 may aggravate the risk of developing URPL by influencing the level of mature miR-423 and its target gene MESDC1.
(Copyright © 2018. Published by Elsevier Inc.)