MiR-423 Coding Region Genetic Polymorphism rs8067576 May Associate With the Risk of Developing Recurrent Spontaneous...

Area of Science:

• Genetics
• Reproductive Biology
• Molecular Biology

Background:

• Previous research identified a link between a single nucleotide polymorphism (SNP) in the miR-423 gene and recurrent spontaneous abortion (RSA).
• The role of other RSA-associated SNPs within the miR-423 gene remained undetermined.

Purpose of the Study:

• To investigate polymorphisms in the coding region of the miR-423 gene.
• To assess the association of these polymorphisms with unexplained recurrent spontaneous abortion (URSA) in Han Chinese women.

Main Methods:

• Genotyping of miR-423 polymorphisms in Han Chinese women with URSA and control subjects.
• Statistical analysis of genotype and allele distributions.
• Assessment of the functional impact of the rs8067576 polymorphism on miR-423 structure, function, and gene regulation.

Main Results:

• Significant differences in genotype and allele distribution of miR-423 rs8067576 were observed between URSA patients and controls.
• A/T heterozygosity at rs8067576 was robustly associated with an elevated incidence of RSA (OR = 1.76).
• The T allele altered pre-miR-423 structure, reduced its stability, promoted cell proliferation, and impaired inhibition of the target gene Pa2g4. The T allele also showed increased susceptibility to mifepristone-induced cell proliferation inhibition.

Conclusions:

• The rs8067576 A > T polymorphism in the miR-423 gene represents a potential genetic susceptibility locus for RSA.
• This polymorphism may increase URSA risk by disrupting mature miR-423 production.