MCM8 rs3761873 和 rs16991617 变异与含铜宫内节育器所致异常子宫出血的关联。

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

机构信息

NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai, China.

Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fujian, China.

出版信息

J Obstet Gynaecol Res. 2022 Feb;48(2):440-447. doi: 10.1111/jog.15101. Epub 2021 Dec 10.

DOI:10.1111/jog.15101

PMID:34889489

Abstract

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 = 0.039 and p = 0.092). rs6022 and rs6029 in F5 gene and rs3761873 and rs16991617 in the MCM8 gene showed strong linkage disequilibrium (R > 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.

摘要

目的

宫内节育器（IUD）是全球广泛使用的避孕方法之一。异常子宫出血（AUB）是 Cu-IUD 最常见的副作用之一。由于 Cu-IUD 用户的 AUB 存在差异，因此出血相关遗传因素的变化可能导致 AUB。本研究旨在确定 Cu-IUD 放置后 AUB 的遗传危险因素。

方法

我们对放置 Cu-IUD 后出现 AUB 的女性进行了病例对照研究（病例：对照=62:59）。使用 Sequenom MassARRAY 对 6 个候选变体进行基因分型。使用 SHEsisPlus 分析基因型和等位基因频率。我们使用 Pearson's Chi-squared 检验分析分类数据，使用 ESEfinder 预测对剪接调控的影响。

结果

MCM8 编码序列变体：rs3761873-A>C 位于所有 19 个外显子的第 7 外显子，rs16991617-A>G 位于第 12 外显子，这两个变体在病例和对照组之间均有显著差异（p=0.039 和 p=0.092）。F5 基因中的 rs6022 和 rs6029 以及 MCM8 基因中的 rs3761873 和 rs16991617 显示出强连锁不平衡（R>0.8）。ESEfinder 表明，MCM8 变体可能影响剪接调控。