Associations of MCM8 rs3761873 and rs16991617 variants with abnormal uterine bleeding induced by copper intrauterine device

Aim: Intrauterine device (IUD) is a commonly used contraceptive method worldwide. Abnormal uterine bleeding (AUB) is one of the most common side effects of Cu-IUDs. Since AUB varies among Cu-IUD users, changes in the bleeding-related genetic factors may contribute to AUB. This study aimed to determine the genetic risk factors of AUB after Cu-IUD insertion.

Methods: We conducted a case-control study on women who experienced AUB after Cu-IUD insertion (case:control = 62:59). Six candidate variants were genotyped using the Sequenom MassARRAY. Genotype and allele frequencies were analyzed using SHEsisPlus. We performed Pearson's Chi-squared test to analyze categorical data, and ESEfinder to predict the impact on splicing regulation.

Results: MCM8 coding sequence variants: rs3761873-A>C was in Exon 7 and rs16991617 A>G was in Exon 12 of all 19 exons, both of which were significantly different between cases and controls (p_allele = 0.039 and p_genotype = 0.092). rs6022 and rs6029 in F5 gene and rs3761873 and rs16991617 in the MCM8 gene showed strong linkage disequilibrium (R² > 0.8). ESEfinder indicated that the variants of MCM8 may affect the splicing regulation.

Conclusions: MCM8 rs376187 and rs16991617 were associated with AUB in Cu-IUDs users. MCM8 may play a role in AUB by regulating functions of reproductive organs and primary ovarian insufficiency. Our findings may improve the understanding of the genetic basis of AUB caused by Cu-IUDs.