Identification of a Functional Susceptibility Variant for Adolescent Idiopathic Scoliosis that Upregulates Early Growth Response 1 (EGR1)-Mediated UNCX Expression.
Yoshiro YonezawaLong GuoHisaya KakinumaNao OtomoSoichiro YoshinoKazuki TakedaMasahiro NakajimaToshiyuki ShirakiYoji OguraYohei TakahashiYoshinao KoikeShohei MinamiKoki UnoNoriaki KawakamiManabu ItoIkuho YonezawaKei WatanabeTakashi KaitoHaruhisa YanagidaHiroshi TaneichiKatsumi HarimayaYuki TaniguchiHideki ShigematsuTakahiro IidaSatoru DemuraRyo SugawaraNobuyuki FujitaMitsuru YagiEijiro OkadaNaobumi HosoganeKatsuki KonoKazuhiro ChibaToshiaki KotaniTsuyoshi SakumaTsutomu AkazawaTeppei SuzukiKotaro NishidaKenichiro KakutaniTaichi TsujiHideki SudoAkira IwataTatsuya SatoSatoshi InamiMasaya NakamuraMorio MatsumotoChikashi C TeraoKota WatanabeHitoshi OkamotoShiro IkegawaPublished in: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research (2022)
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).
Keyphrases
- binding protein
- transcription factor
- poor prognosis
- genome wide association
- genome wide
- copy number
- healthcare
- public health
- dna binding
- mental health
- bone mineral density
- long non coding rna
- dna methylation
- genome wide association study
- genome wide identification
- ultrasound guided
- health promotion
- molecular dynamics simulations
- nucleic acid