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The human ATF1 rs11169571 polymorphism increases essential hypertension risk through modifying miRNA binding
Author(s) -
Yang Sibao,
Gao Yongjian,
Liu Guohui,
Li Jiayu,
Shi Kaiyao,
Du Beibei,
Si Daoyuan,
Yang Ping
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.06.029
Subject(s) - nox1 , single nucleotide polymorphism , biology , microrna , allele , microbiology and biotechnology , snp , three prime untranslated region , reporter gene , untranslated region , gene expression , gene , genetics , nadph oxidase , messenger rna , reactive oxygen species , genotype
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.