Novel genetic variants linked to prelabor rupture of membranes among Chinese pregnant women

Hui Kan; Haiyan Liu; Yutong Mu; Yijie Li; Miao Zhang; Yanmin Cao; Yao Dong; Yaxin Li; Kailin Wang; Qing Li; Anqun Hu; Yingjie Zheng

doi:10.1016/j.placenta.2023.04.007

Novel genetic variants linked to prelabor rupture of membranes among Chinese pregnant women

Placenta. 2023 Jun:137:14-22. doi: 10.1016/j.placenta.2023.04.007. Epub 2023 Apr 7.

Authors

Hui Kan¹, Haiyan Liu², Yutong Mu¹, Yijie Li¹, Miao Zhang¹, Yanmin Cao¹, Yao Dong¹, Yaxin Li¹, Kailin Wang¹, Qing Li³, Anqun Hu⁴, Yingjie Zheng⁵

Affiliations

¹ Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China; Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning, Fudan University, Shanghai, 200032, China.
² Department of Clinical Laboratory, Anqing Municipal Hospital, Anqing, 246003, China; Department of Blood Transfusion, Anqing Municipal Hospital, Anqing, 246003, China.
³ Department of Obstetrics and Gynecology, Anqing Municipal Hospital, Anqing, 246003, China. Electronic address: liqing03027@163.com.
⁴ Department of Clinical Laboratory, Anqing Municipal Hospital, Anqing, 246003, China. Electronic address: haq0828@hotmail.com.
⁵ Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China; Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning, Fudan University, Shanghai, 200032, China; Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai, 200032, China. Electronic address: yjzheng@fudan.edu.cn.

PMID: 37054626
DOI: 10.1016/j.placenta.2023.04.007

Abstract

Introduction: The etiology of prelabor rupture of membranes (PROM), either preterm or term PROM (PPROM or TPROM), remains largely unknown. This study aimed to investigate the association between maternal genetic variants (GVs) and PROM and further establish a GV-based prediction model for PROM.

Methods: In this case-cohort study (n = 1166), Chinese pregnant women with PPROM (n = 51), TPROM (n = 283) and controls (n = 832) were enrolled. A weighted Cox model was applied to identify the GVs (single nucleotide polymorphisms [SNPs], insertions/deletions, and copy number variants) associated with either PPROM or TPROM. Gene set enrichment analysis (GSEA) was to explore the mechanisms. The suggestively significant GVs were applied to establish a random forest (RF) model.

Results: PTPRT variants (rs117950601, P = 4.37 × 10^-9; rs147178603, P = 8.98 × 10^-9) and SNRNP40 variant (rs117573344, P = 2.13 × 10^-8) were associated with PPROM. STXBP5L variant (rs10511405, P = 4.66 × 10^-8) was associated with TPROM. GSEA results showed that genes associated with PPROM were enriched in cell adhesion, and TPROM in ascorbate and glucuronidation metabolism. The area under the receiver operating characteristic curve of SNP-based RF model for PPROM was 0.961, with a sensitivity of 100.0% and specificity of 83.3%.

Discussion: Maternal GVs in PTPRT and SNRNP40 were associated with PPROM, and GV in STXBP5L was associated with TPROM. Cell adhesion participated in PPROM, while ascorbate and glucuronidation metabolism contributed in TPROM. The PPROM might be well predicted using the SNP-based RF model.

Keywords: Fetal membranes; Genetic variants; Random forest model; Rupture; Single nucleotide polymorphisms.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cohort Studies
East Asian People
Female
Fetal Membranes, Premature Rupture* / genetics
Fetal Membranes, Premature Rupture* / metabolism
Humans
Infant, Newborn
Pregnancy
Pregnant Women*

Substances

PTPRT protein, human
SNRNP40 protein, human
STXBP5L protein, human

Supplementary concepts

Preterm Premature Rupture of the Membranes