Identification of a Functional Susceptibility Variant for Adolescent Idiopathic Scoliosis that Upregulates Early Growth Response 1 (EGR1)-Mediated UNCX Expression.
CELL/TISSUE SIGNALING-TRANSCRIPTION FACTORS
DISEASES AND DISORDERS OF/RELATED TO BONE
GENETIC ANIMAL MODELS
GENETIC RESEARCH
HUMAN ASSOCIATION STUDIES
Journal
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
ISSN: 1523-4681
Titre abrégé: J Bone Miner Res
Pays: United States
ID NLM: 8610640
Informations de publication
Date de publication:
01 2023
01 2023
Historique:
revised:
23
10
2022
received:
22
07
2022
accepted:
03
11
2022
pubmed:
8
11
2022
medline:
10
1
2023
entrez:
7
11
2022
Statut:
ppublish
Résumé
Adolescent idiopathic scoliosis (AIS) is a serious health problem affecting 3% of live births all over the world. Many loci associated with AIS have been identified by previous genome wide association studies, but their biological implication remains mostly unclear. In this study, we evaluated the AIS-associated variants in the 7p22.3 locus by combining in silico, in vitro, and in vivo analyses. rs78148157 was located in an enhancer of UNCX, a homeobox gene and its risk allele upregulated the UNCX expression. A transcription factor, early growth response 1 (EGR1), transactivated the rs78148157-located enhancer and showed a higher binding affinity for the risk allele of rs78148157. Furthermore, zebrafish larvae with UNCX messenger RNA (mRNA) injection developed body curvature and defective neurogenesis in a dose-dependent manner. rs78148157 confers the genetic susceptibility to AIS by enhancing the EGR1-regulated UNCX expression. © 2022 American Society for Bone and Mineral Research (ASBMR).
Substances chimiques
Transcription Factors
0
Egr1 protein, zebrafish
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
144-153Informations de copyright
© 2022 American Society for Bone and Mineral Research (ASBMR).
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