TIMP2 rs2277698 polymorphism associated with adverse IVF outcomes in Han Chinese women.

IF 3.9 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Frontiers in Endocrinology Pub Date : 2025-03-13 eCollection Date: 2025-01-01 DOI:10.3389/fendo.2025.1542534

Chun-I Lee, Yu-Jen Lee, Tsung-Hsien Lee, Chi-Ying Lee, Hui-Mei Tsao, En-Hui Cheng, Chun-Chia Huang, Shun-Fa Yang, Maw-Sheng Lee

{"title":"TIMP2 rs2277698 polymorphism associated with adverse IVF outcomes in Han Chinese women.","authors":"Chun-I Lee, Yu-Jen Lee, Tsung-Hsien Lee, Chi-Ying Lee, Hui-Mei Tsao, En-Hui Cheng, Chun-Chia Huang, Shun-Fa Yang, Maw-Sheng Lee","doi":"10.3389/fendo.2025.1542534","DOIUrl":null,"url":null,"abstract":"Background: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are critical regulators of extracellular matrix (ECM) proteolysis and play a pivotal role in trophoblast invasion during embryo implantation. This study aimed to investigate the effects of single-nucleotide polymorphisms (SNPs) in MMP and TIMP genes on clinical outcomes in women undergoing in vitro fertilization (IVF).Methods: This retroprospective study included 1014 women undergoing their first fresh IVF cycle without donor eggs at Lee Women's Hospital between January 2014 and December 2015. Peripheral blood samples were collected from all participants for DNA extraction and SNP genotyping using real-time polymerase chain reaction. The study focused on three SNPs: TIMP1 (rs4898 C/T), TIMP2 (rs2277698 C/T), and MMP2 (rs243865 C/T). Associations between these SNPs and IVF outcomes, including clinical pregnancy, embryo implantation, abortion, and live birth rates, were analyzed.Results: Among 560 patients analyzed, no significant differences were observed in baseline characteristics between the live birth and non-live birth groups. However, the minor alleles (CT+TT) of MMP2 (rs243865) and TIMP2 (rs2277698) were significantly more frequent in the non-live birth group (MMP2: 24.4% vs. 17.7%, p = 0.044; TIMP2: 48.1% vs. 34.4%, p = 0.001). In contrast, no significant differences in the genotype distribution of TIMP1 (rs4898) were noted between the groups. Logistic regression analysis identified the minor T allele of TIMP2 as a significant predictor of non-live birth (adjusted odds ratio: 1.725; 95% CI: 1.217-2.445; p = 0.002). Combined genotypes of MMP2/TIMP2, such as CC/CT+TT and CT+TT/CT+TT, were associated with an increased risk of non-live birth, even after adjusting for covariates.Conclusions: The study demonstrates that the minor T allele of TIMP2 (rs2277698 C/T) is associated with poor IVF outcomes, particularly non-live birth. This finding highlights the potential role of genetic variations in TIMP2 in influencing clinical outcomes of IVF. Further research is warranted to elucidate the underlying mechanisms in larger and more diverse populations.","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"16 ","pages":"1542534"},"PeriodicalIF":3.9000,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948279/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Endocrinology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fendo.2025.1542534","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are critical regulators of extracellular matrix (ECM) proteolysis and play a pivotal role in trophoblast invasion during embryo implantation. This study aimed to investigate the effects of single-nucleotide polymorphisms (SNPs) in MMP and TIMP genes on clinical outcomes in women undergoing in vitro fertilization (IVF).

Methods: This retroprospective study included 1014 women undergoing their first fresh IVF cycle without donor eggs at Lee Women's Hospital between January 2014 and December 2015. Peripheral blood samples were collected from all participants for DNA extraction and SNP genotyping using real-time polymerase chain reaction. The study focused on three SNPs: TIMP1 (rs4898 C/T), TIMP2 (rs2277698 C/T), and MMP2 (rs243865 C/T). Associations between these SNPs and IVF outcomes, including clinical pregnancy, embryo implantation, abortion, and live birth rates, were analyzed.

Results: Among 560 patients analyzed, no significant differences were observed in baseline characteristics between the live birth and non-live birth groups. However, the minor alleles (CT+TT) of MMP2 (rs243865) and TIMP2 (rs2277698) were significantly more frequent in the non-live birth group (MMP2: 24.4% vs. 17.7%, p = 0.044; TIMP2: 48.1% vs. 34.4%, p = 0.001). In contrast, no significant differences in the genotype distribution of TIMP1 (rs4898) were noted between the groups. Logistic regression analysis identified the minor T allele of TIMP2 as a significant predictor of non-live birth (adjusted odds ratio: 1.725; 95% CI: 1.217-2.445; p = 0.002). Combined genotypes of MMP2/TIMP2, such as CC/CT+TT and CT+TT/CT+TT, were associated with an increased risk of non-live birth, even after adjusting for covariates.

Conclusions: The study demonstrates that the minor T allele of TIMP2 (rs2277698 C/T) is associated with poor IVF outcomes, particularly non-live birth. This finding highlights the potential role of genetic variations in TIMP2 in influencing clinical outcomes of IVF. Further research is warranted to elucidate the underlying mechanisms in larger and more diverse populations.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Frontiers in Endocrinology Medicine-Endocrinology, Diabetes and Metabolism

CiteScore

5.70

自引率

9.60%

发文量

3023

审稿时长

14 weeks

期刊介绍： Frontiers in Endocrinology is a field journal of the "Frontiers in" journal series. In today’s world, endocrinology is becoming increasingly important as it underlies many of the challenges societies face - from obesity and diabetes to reproduction, population control and aging. Endocrinology covers a broad field from basic molecular and cellular communication through to clinical care and some of the most crucial public health issues. The journal, thus, welcomes outstanding contributions in any domain of endocrinology. Frontiers in Endocrinology publishes articles on the most outstanding discoveries across a wide research spectrum of Endocrinology. The mission of Frontiers in Endocrinology is to bring all relevant Endocrinology areas together on a single platform.