Integrative genetic, genomic and transcriptomic analysis of heat shock protein and nuclear hormone receptor gene associations with spontaneous preterm birth.

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.

Tiensuu, Heli (author)
Haapalainen, Antti M (author)
Pasanen, Anu (author)
Tissarinen, Pinja (author)
Karjalainen, Minna K (author)
Zhang, Ge (author)
Christensen, Kaare (author)
Ryckman, Kelli K (author)
Jacobsson, Bo,1960Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi,Institute of Clinical Sciences, Department of Obstetrics and Gynecology(Swepub:gu)xjacbo (author)
Murray, Jeffrey C (author)
Kingsmore, Stephen F (author)
Hallman, Mikko (author)
Muglia, Louis J (author)
Rämet, Mika (author)
Göteborgs universitetInstitutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi (creator_code:org_t)

By the author/editor: Huusko, Johanna ...; Tiensuu, Heli; Haapalainen, Ant ...; Pasanen, Anu; Tissarinen, Pinj ...; Karjalainen, Min ...; show more...; Zhang, Ge; Christensen, Kaa ...; Ryckman, Kelli K; Jacobsson, Bo, 1 ...; Murray, Jeffrey ...; Kingsmore, Steph ...; Hallman, Mikko; Muglia, Louis J; Rämet, Mika; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Obstetrics Gynae ...

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