title: The human ATF1 rs11169571 polymorphism increases essential hypertension risk through modifying miRNA binding.
abstract: Activating transcription factor 1 (ATF1) may be involved in essential hypertension (EH) by induction of NADPH oxidase 1 (NOX1) and radical oxygen species (ROSs) production. Abnormal expression of ATF1 was found in EH in previous microarray analysis. Here we tested whether a single nucleotide polymorphism (SNP) located in the 3'-untranslated region (3'UTR) of ATF1 was associated with EH susceptibility by affecting microRNA (miRNA) binding. In silico analysis indicated that rs11169571 (T>C) was a candidate SNP to modulate miRNA: ATF1 mRNA complex, with the greatest changed energy for hsa-miR-1283, and the luciferase reporter analysis showed that miR-1283 inhibited the activity of the reporter vector carrying -T allele, but not the -C allele. In addition, inhibition of miR-1283 in HA-VSMCs enhanced the expression of ATF1 mRNA as well as the ROS levels. Further case-control study showed that rs11169571 was significantly associated with increased risk of EH. Finally, we observed an increased ATF1 protein level in peripheral blood of EH patients with CC carriers compared to TT carriers of rs11169571, with an intermediate ATF1 level in TC carriers. These results suggested that rs11169571 of ATF1 gene may be associated with EH, and the SNP-modified posttranscriptional gene regulation by miRNAs could be a potentially pathogenetic mechanism of EH.
authors.affiliation: Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun, China.
authors.forename: Sibao
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Gastrointestinal Surgery, China-Japan Union Hospital, Jilin University, Changchun, China.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun, China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun, China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun, China.
authors.forename: Kaiyao
authors.initials: K
authors.lastname: Shi
authors.affiliation: Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun, China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Du
authors.affiliation: Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun, China.
authors.forename: Daoyuan
authors.initials: D
authors.lastname: Si
authors.affiliation: Department of Cardiology, China-Japan Union Hospital, Jilin University, Changchun, China. Electronic address: pyang@jlu.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
mesh_terms: D020413:3' Untranslated Regions; D051697:Activating Transcription Factor 1 / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002478:Cells, Cultured; D002681:China; D019295:Computational Biology; D000075222:Essential Hypertension; D005103:Expert Systems; D005260:Female; D020868:Gene Silencing; D017930:Genes, Reporter; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D008957:Models, Genetic; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C531110:ATF1 protein, human; D051697:Activating Transcription Factor 1; C581550:MIRN1283 microRNA, human; D035683:MicroRNAs; D017382:Reactive Oxygen Species
keywords: Activating transcription factor 1; Association study; Essential hypertension; Single nucleotide polymorphism; microRNA-1283