BRCA1/2 Polymorphisms and the Risk of Recurrent Implantation Failure in Korean Women

Recurrent implantation failure (RIF) is a major cause of unsuccessful assisted reproduction, yet its genetic basis remains poorly defined. Because BRCA1 and BRCA2 are central to homologous recombination-mediated repair of DNA double-strand breaks, we examined whether common variants in these genes are associated with RIF. Seven BRCA1/2 single-nucleotide polymorphisms, prioritized from whole-exome sequencing data, were genotyped in 128 women with RIF and 330 controls with proven natural fertility, and associations were estimated by age-adjusted logistic regression with false discovery rate (FDR) correction. The BRCA2 rs1799943 A allele was associated with lower odds of RIF under the heterozygous (adjusted odds ratio [AOR] 0.445, FDR q = 0.006) and dominant (AOR 0.443, q = 0.004) models; no other variant remained associated after correction. In exploratory analyses of the same participants, this inverse association was largely confined to carriers of the BRCA1 rs12516 A allele (interaction q = 0.003), the BRCA2 haplotype carrying the rs1799943 A allele was associated with lower odds of RIF (AOR 0.551, q = 0.012), and nominal associations of genotype combinations involving rs15869 were not supported by formal interaction testing. These findings identify rs1799943 as a candidate variant associated with RIF that warrants replication and functional investigation.