We investigated whether microRNA (miRNA) polymorphisms (miR-146aC>G, miR-196a2T>C, and miR-499A>G) confer risk of premature ovarian failure (POF) in Korean women. DNA samples from 136 patients with POF and 234 controls were genotyped for the 3 miRNA single-nucleotide polymorphisms by polymerase chain reaction–restriction fragment length polymorphism. The miR-146aCG/miR-196a2TC combined genotype was less frequent in patients than in controls (P < .05), conferring less susceptibility. Using haplotype-based multifactor dimensionality reduction analysis, the C-C-A and G-T-A inferred haplotypes (miR-146a/miR-196a2/miR-499) were less frequent in patients, suggesting protective effects (P < .05 for each), whereas the C-T-A and G-C-A haplotypes were more frequent in patients (P < .05 for each). The C-T and G-C haplotypes (miR-146a/miR-196a2) were more frequent in patients, whereas the C-C and G-T haplotypes were less frequent in patients (P < .05 for each). However, none of the 3 miRNA polymorphisms alone was associated with POF risk. Our findings suggest that putative gene–gene interaction between miR-146 and miR-196a2 may be involved in POF development.
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