MiR-423 Coding Region Genetic Polymorphism rs8067576 May Associate With the Risk of Developing Recurrent Spontaneous Abortion: A Case-Control Study in a Chinese Han Population

Abstract

Background

Our previous study has identified an association of a single nucleotide polymorphism (SNP) in the miR-423 gene with recurrent spontaneous abortion (RSA). The presence of additional RSA-linked SNPs in the miR-423 gene remains unclear.

Methods

We evaluated polymorphisms in the coding region of miR-423 in Han Chinese women with unexplained RSA (URSA).

Results

Significant differences were observed in the genotype and allele distribution of miR-423 rs8067576 between patients with RSA and control subjects. A robust association was found between an elevated RSA incidence and the presence of A/T heterozygosity in miR-423 rs8067576, with an odds ratio (OR) of 1.76 (95% confidence interval [CI]: 1.26 to 2.47, p = 0.000292). The rare allele T in the pre-miR-423 sequence was shown to cause a discernible structural change and a reduced ΔG value. Compared with the A allele, the rare T allele promoted cell proliferation. Furthermore, compared with the T allele, the A allele in the rs8067576 polymorphism exhibited a greater ability to inhibit the translation of proliferation-associated 2 group 4 (Pa2g4), which is the functional target of miR-423. The T allele in the rs8067576 polymorphism was also found to be more susceptible to the inhibition of cell proliferation induced by mifepristone.

Conclusions

The rs8067576 A > T polymorphism in the miR-423 gene may serve as a genetic susceptibility locus for RSA. This polymorphism appears to contribute to an increased risk of acquiring URSA in humans by destroying mature miR-423.