Integrative genetic, genomic and transcriptomic analysis of heat shock protein and nuclear hormone receptor gene associations with spontaneous preterm birth.
Adult
Female
HSP70 Heat-Shock Proteins
/ genetics
Heat-Shock Proteins
/ genetics
Humans
Infant, Premature
Male
Molecular Chaperones
/ genetics
Nuclear Receptor Subfamily 1, Group F, Member 1
/ genetics
Placenta
/ metabolism
Pregnancy
Premature Birth
/ genetics
RNA-Binding Proteins
/ genetics
Receptors, Androgen
/ genetics
Transcriptome
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
24 08 2021
24 08 2021
Historique:
received:
10
05
2021
accepted:
09
08
2021
entrez:
25
8
2021
pubmed:
26
8
2021
medline:
3
11
2021
Statut:
epublish
Résumé
Heat shock proteins are involved in the response to stress including activation of the immune response. Elevated circulating heat shock proteins are associated with spontaneous preterm birth (SPTB). Intracellular heat shock proteins act as multifunctional molecular chaperones that regulate activity of nuclear hormone receptors. Since SPTB has a significant genetic predisposition, our objective was to identify genetic and transcriptomic evidence of heat shock proteins and nuclear hormone receptors that may affect risk for SPTB. We investigated all 97 genes encoding members of the heat shock protein families and all 49 genes encoding nuclear hormone receptors for their potential role in SPTB susceptibility. We used multiple genetic and genomic datasets including genome-wide association studies (GWASs), whole-exome sequencing (WES), and placental transcriptomics to identify SPTB predisposing factors from the mother, infant, and placenta. There were multiple associations of heat shock protein and nuclear hormone receptor genes with SPTB. Several orthogonal datasets supported roles for SEC63, HSPA1L, SACS, RORA, and AR in susceptibility to SPTB. We propose that suppression of specific heat shock proteins promotes maintenance of pregnancy, whereas activation of specific heat shock protein mediated signaling may disturb maternal-fetal tolerance and promote labor.
Identifiants
pubmed: 34429451
doi: 10.1038/s41598-021-96374-9
pii: 10.1038/s41598-021-96374-9
pmc: PMC8384995
doi:
Substances chimiques
AR protein, human
0
HSP70 Heat-Shock Proteins
0
HSPA1L protein, human
0
Heat-Shock Proteins
0
Molecular Chaperones
0
Nuclear Receptor Subfamily 1, Group F, Member 1
0
RNA-Binding Proteins
0
RORA protein, human
0
Receptors, Androgen
0
SACS protein, human
0
SEC63 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
17115Subventions
Organisme : NHGRI NIH HHS
ID : U01 HG004446
Pays : United States
Organisme : NINDS NIH HHS
ID : U01 NS047537
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD101669
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004423
Pays : United States
Organisme : NIEHS NIH HHS
ID : N01ES75558
Pays : United States
Informations de copyright
© 2021. The Author(s).
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