Rare SNP rs12731181 in the miR-590-3p Target Site of the Prostaglandin F2α Receptor Gene Confers Risk for Essential Hypertension in the Han Chinese Population

Bing Xiao; Shui-Ming Gu; Mulin Jun Li; Jun Li; Bo Tao; Yuanyang Wang; Yan Wang; Shengkai Zuo; Yujun Shen; Yu Yu; Di Chen; Guilin Chen; Deping Kong; Juan Tang; Qian Liu; Dong-Rui Chen; Yong Liu; Sara Alberti; Melania Dovizio; Raffaele Landolfi; Luciana Mucci; Pei-Zhi Miao; Pingjin Gao; Ding-Liang Zhu; Junwen Wang; Bin Li; Paola Patrignani; Ying Yu

doi:10.1161/ATVBAHA.115.305445

Rare SNP rs12731181 in the miR-590-3p Target Site of the Prostaglandin F2α Receptor Gene Confers Risk for Essential Hypertension in the Han Chinese Population

Arterioscler Thromb Vasc Biol. 2015 Jul;35(7):1687-95. doi: 10.1161/ATVBAHA.115.305445. Epub 2015 May 14.

Authors

Bing Xiao¹, Shui-Ming Gu¹, Mulin Jun Li¹, Jun Li¹, Bo Tao¹, Yuanyang Wang¹, Yan Wang¹, Shengkai Zuo¹, Yujun Shen¹, Yu Yu¹, Di Chen¹, Guilin Chen¹, Deping Kong¹, Juan Tang¹, Qian Liu¹, Dong-Rui Chen¹, Yong Liu¹, Sara Alberti¹, Melania Dovizio¹, Raffaele Landolfi¹, Luciana Mucci¹, Pei-Zhi Miao¹, Pingjin Gao¹, Ding-Liang Zhu¹, Junwen Wang¹, Bin Li¹, Paola Patrignani¹, Ying Yu²

Affiliations

¹ From the Key Laboratory of Food Safety Research (B.X., Y.W., S.Z., Y.S., Yu Yu, D.C., G.C., D.K., J.T., Q.L., Ying Yu), Key Laboratory of Nutrition and Metabolism (Y.L.), Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; Department of Cardiology, Shanghai Xuhui Central Hospital, Shanghai, China (S.-M.G., P.-Z.M.); Department of Biochemistry and Centre for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China (M.J.L., J.W.); Shenzhen Institute of Research & Innovation, The University of Hong Kong, Shenzhen, China (J.W.); Orthopedic Institute, Soochow University, Jiangsu, China (J.L., B.L.); College of Basic Medicine, Gannan Medical University, Ganzhou, China (B.T.); Shanghai Key Laboratory of Vascular Biology and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Y.W., D.-R.C., P.G., D.-L.Z.); Department of Neuroscience, Imaging and Clinical Sciences and CeSI, "G. d'Annunzio" University, Chieti, Italy (S.A., M.D., P.P.); Department of Medical Science, Catholic University, Rome, Italy (R.L., L.M.); Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China (Ying Yu); and State Key Laboratory for Medical Genomics, School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China (B.X.).
² From the Key Laboratory of Food Safety Research (B.X., Y.W., S.Z., Y.S., Yu Yu, D.C., G.C., D.K., J.T., Q.L., Ying Yu), Key Laboratory of Nutrition and Metabolism (Y.L.), Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; Department of Cardiology, Shanghai Xuhui Central Hospital, Shanghai, China (S.-M.G., P.-Z.M.); Department of Biochemistry and Centre for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China (M.J.L., J.W.); Shenzhen Institute of Research & Innovation, The University of Hong Kong, Shenzhen, China (J.W.); Orthopedic Institute, Soochow University, Jiangsu, China (J.L., B.L.); College of Basic Medicine, Gannan Medical University, Ganzhou, China (B.T.); Shanghai Key Laboratory of Vascular Biology and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (Y.W., D.-R.C., P.G., D.-L.Z.); Department of Neuroscience, Imaging and Clinical Sciences and CeSI, "G. d'Annunzio" University, Chieti, Italy (S.A., M.D., P.P.); Department of Medical Science, Catholic University, Rome, Italy (R.L., L.M.); Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China (Ying Yu); and State Key Laboratory for Medical Genomics, School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China (B.X.). yuying@sibs.ac.cn.

PMID: 25977569
DOI: 10.1161/ATVBAHA.115.305445

Abstract

Objective: To investigate whether rs12731181 (A→G) interrupted miR-590-3p-mediated suppression of the prostaglandin F2α receptor (FP) and whether it is associated with essential hypertension in the Chinese population.

Approach and results: We found that miR-590-3p regulates human FP gene expression by binding to its 3'-untranslated region. rs12731181 (A→G) altered the binding affinity between miR-590-3p and its FP 3'-untranslated region target, thus reducing the suppression of FP expression, which, in turn, enhanced FP receptor-mediated contractility of vascular smooth muscle cells. Overexpression of FP augmented vascular tone and elevated blood pressure in mice. An association study was performed to analyze the relationship between the FP gene and essential hypertension in the Han Chinese population. The results indicated that the rs12731181 G allele was associated with susceptibility to essential hypertension. Carriers of the AG genotype exhibited significantly higher blood pressure than those of the AA genotype. FP gene expression was significantly higher in human peripheral leukocytes from individuals with the AG genotype than that in leukocytes from individuals with the AA genotype.

Conclusions: rs12731181 in the seed region of the miR-590-3p target site is associated with increased risk of essential hypertension and represents a new paradigm for FP involvement in blood pressure regulation.

Keywords: essential; hypertension; microRNAs; polymorphism; prostaglandin F2α receptor; single nucleotide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3' Untranslated Regions
Animals
Asian People / genetics*
Binding Sites
China / ethnology
Essential Hypertension
Genetic Predisposition to Disease
Humans
Hypertension / genetics*
Mice
MicroRNAs / genetics*
Polymorphism, Single Nucleotide
Receptors, Prostaglandin / genetics*
Transcription, Genetic

Substances

3' Untranslated Regions
MIRN590 microRNA, human
MicroRNAs
Receptors, Prostaglandin
prostaglandin F2alpha receptor