(Epi)genetic variants of the sarcomere-desmosome are associated with premature utero-contraction in spontaneous preterm labor
Spontaneous preterm birth is a syndrome with clinical and genetic heterogeneity. Few studies have focused on the genetic and epigenetic defects and pathogenic mechanisms associated with premature uterine contraction in spontaneous preterm birth. The objective of this study was to investigate the (ep...
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Elsevier
2021-03-01
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Series: | Environment International |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412021000064 |
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doaj-c69b7a912f8e4ffc96054dff054f4f40 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jie Wang Xiucui Luo Jing Pan Xiaoyan Dong Xiujuan Tian Zhihua Tu Weina Ju Meijiao Zhang Mei Zhong Charles De Chen Michael Flory Yong Wang W. Ted Brown Nanbert Zhong |
spellingShingle |
Jie Wang Xiucui Luo Jing Pan Xiaoyan Dong Xiujuan Tian Zhihua Tu Weina Ju Meijiao Zhang Mei Zhong Charles De Chen Michael Flory Yong Wang W. Ted Brown Nanbert Zhong (Epi)genetic variants of the sarcomere-desmosome are associated with premature utero-contraction in spontaneous preterm labor Environment International Preterm birth Uterine contraction Sarcomere Desmosome Multi-omic study Systems biology |
author_facet |
Jie Wang Xiucui Luo Jing Pan Xiaoyan Dong Xiujuan Tian Zhihua Tu Weina Ju Meijiao Zhang Mei Zhong Charles De Chen Michael Flory Yong Wang W. Ted Brown Nanbert Zhong |
author_sort |
Jie Wang |
title |
(Epi)genetic variants of the sarcomere-desmosome are associated with premature utero-contraction in spontaneous preterm labor |
title_short |
(Epi)genetic variants of the sarcomere-desmosome are associated with premature utero-contraction in spontaneous preterm labor |
title_full |
(Epi)genetic variants of the sarcomere-desmosome are associated with premature utero-contraction in spontaneous preterm labor |
title_fullStr |
(Epi)genetic variants of the sarcomere-desmosome are associated with premature utero-contraction in spontaneous preterm labor |
title_full_unstemmed |
(Epi)genetic variants of the sarcomere-desmosome are associated with premature utero-contraction in spontaneous preterm labor |
title_sort |
(epi)genetic variants of the sarcomere-desmosome are associated with premature utero-contraction in spontaneous preterm labor |
publisher |
Elsevier |
series |
Environment International |
issn |
0160-4120 |
publishDate |
2021-03-01 |
description |
Spontaneous preterm birth is a syndrome with clinical and genetic heterogeneity. Few studies have focused on the genetic and epigenetic defects and pathogenic mechanisms associated with premature uterine contraction in spontaneous preterm birth. The objective of this study was to investigate the (epi)genetic variations associated with premature uterine contraction of spontaneous preterm birth. A systems biology approach with an integrated multiomic study was employed. Biobanked pregnancy tissues selected from a pregnancy cohort were subjected to genomic, transcriptomic, methylomic, and proteomic studies, with a focus on genetic loci/genes related to uterine muscle contraction, specifically, genes associated with sarcomeres and desmosomes. Thirteen single nucleotide variations and pathogenic variants were identified in the sarcomere gene, TTN, which encodes the protein Titin, from 146 women with spontaneous preterm labor. Differential expression profiles of five long non-coding RNAs were identified from loci that overlap with four sarcomeric genes. Longitudinally, the long non-coding RNA of gene TPM3 that encodes the protein tropomysin 3 was found to significantly regulate the mRNA of TPM3 in the placenta, compared to maternal blood. The majority of genome methylation profiles related to premature uterine contraction were also identified in the CpG promoters of sarcomeric genes/loci. Differential expression profiles of mRNAs associated with premature uterine contraction showed 22 genes associated with sarcomeres and three with desmosomes. The results demonstrated that premature uterine contraction was associated mainly with pathogenic variants of the TTN gene and with transcriptomic variations of sarcomeric premature uterine contraction genes. This association is likely regulated by epigenetic factors, including methylation and long non-coding RNAs. |
topic |
Preterm birth Uterine contraction Sarcomere Desmosome Multi-omic study Systems biology |
url |
http://www.sciencedirect.com/science/article/pii/S0160412021000064 |
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doaj-c69b7a912f8e4ffc96054dff054f4f402021-02-05T15:29:41ZengElsevierEnvironment International0160-41202021-03-01148106382(Epi)genetic variants of the sarcomere-desmosome are associated with premature utero-contraction in spontaneous preterm laborJie Wang0Xiucui Luo1Jing Pan2Xiaoyan Dong3Xiujuan Tian4Zhihua Tu5Weina Ju6Meijiao Zhang7Mei Zhong8Charles De Chen9Michael Flory10Yong Wang11W. Ted Brown12Nanbert Zhong13Hainan Provincial Hospital for Maternal and Children’s Health, Haikou, Hainan, China; Preterm Birth International Collaborative, USACenter of Translational Research, Lianyungang Municipal Hospital for Maternal and Children’s Health, Lianyungang, Jiangsu Province, ChinaCenter of Translational Research, Lianyungang Municipal Hospital for Maternal and Children’s Health, Lianyungang, Jiangsu Province, ChinaNew York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA; Shanghai Children’s Hospital, Shanghai Jiaotong University, Shanghai, ChinaSanya Maternity and Child Care Hospital, Sanya, Hainan, China; Corresponding authorsat: Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road Staten Island, NY 10314, USA.Hainan Provincial Hospital for Maternal and Children’s Health, Haikou, Hainan, ChinaNew York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USACenter of Translational Research, Lianyungang Municipal Hospital for Maternal and Children’s Health, Lianyungang, Jiangsu Province, ChinaNanfang Hospital, Southern Medical University, Guangzhou, ChinaThe Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaNew York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USADepartment of Obstetrics and Gynecology, Washington University, St. Louis, MO, USA; Preterm Birth International Collaborative, USANew York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USANew York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA; Preterm Birth International Collaborative, USA; Corresponding authorsat: Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road Staten Island, NY 10314, USA.Spontaneous preterm birth is a syndrome with clinical and genetic heterogeneity. Few studies have focused on the genetic and epigenetic defects and pathogenic mechanisms associated with premature uterine contraction in spontaneous preterm birth. The objective of this study was to investigate the (epi)genetic variations associated with premature uterine contraction of spontaneous preterm birth. A systems biology approach with an integrated multiomic study was employed. Biobanked pregnancy tissues selected from a pregnancy cohort were subjected to genomic, transcriptomic, methylomic, and proteomic studies, with a focus on genetic loci/genes related to uterine muscle contraction, specifically, genes associated with sarcomeres and desmosomes. Thirteen single nucleotide variations and pathogenic variants were identified in the sarcomere gene, TTN, which encodes the protein Titin, from 146 women with spontaneous preterm labor. Differential expression profiles of five long non-coding RNAs were identified from loci that overlap with four sarcomeric genes. Longitudinally, the long non-coding RNA of gene TPM3 that encodes the protein tropomysin 3 was found to significantly regulate the mRNA of TPM3 in the placenta, compared to maternal blood. The majority of genome methylation profiles related to premature uterine contraction were also identified in the CpG promoters of sarcomeric genes/loci. Differential expression profiles of mRNAs associated with premature uterine contraction showed 22 genes associated with sarcomeres and three with desmosomes. The results demonstrated that premature uterine contraction was associated mainly with pathogenic variants of the TTN gene and with transcriptomic variations of sarcomeric premature uterine contraction genes. This association is likely regulated by epigenetic factors, including methylation and long non-coding RNAs.http://www.sciencedirect.com/science/article/pii/S0160412021000064Preterm birthUterine contractionSarcomereDesmosomeMulti-omic studySystems biology |