Association of AGTR1 Promoter Methylation Levels with Essential Hypertension Risk: A Matched Case-Control Study

被引:23
作者
Fan, Rui [1 ]
Mao, Shuqi [1 ]
Zhong, Fade [2 ]
Gong, Minli [3 ]
Yin, Fengying [4 ]
Hao, Lingmei [3 ]
Zhang, Lina [1 ]
机构
[1] Ningbo Univ, Sch Med, Zhejiang Prov Key Lab Pathophysiol, Dept Prevent Med, Ningbo 315211, Zhejiang, Peoples R China
[2] Cent Blood Stn Ningbo, Ningbo, Zhejiang, Peoples R China
[3] Seventh Hosp Ningbo, Clin Lab, Ningbo 315211, Zhejiang, Peoples R China
[4] First Hosp Ningbo, Clin Lab, Ningbo, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
AGTR1; Epigenetic; Essential hypertension; Methylation; Promoter; RENIN-ANGIOTENSIN SYSTEM; SERUM URIC-ACID; DNA METHYLATION; BLOOD-PRESSURE; GENE PROMOTER; EXPRESSION; RECEPTOR;
D O I
10.1159/000442366
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The purpose of the present study was to investigate whether methylation of the angiotensin II type 1 receptor (AGTR1) promoter contributed to the risk of essential hypertension (EH). A total of 96 EH cases and 96 gender-and age-matched healthy controls were recruited. Methylation of 8 CpG dinucleotides (CpG1-8) in the AGTR1 promoter was examined using the bisulphite pyrosequencing technology. Three CpG dinucleotides (CpG6-8) could not be well sequenced, therefore only the remaining 5 CpG sites were analysed. A significantly lower CpG1 methylation level was identified in EH cases than in controls (cases vs. controls: 6.74 +/- 4.32% vs. 9.66 +/- 5.45%, p = 0.007), and no significant association was observed in the remaining analyses. In addition, significantly lower CpG1 (p = 0.028) and higher CpG2 (p = 0.032) methylation levels were observed in males than in females. In the breakdown association test by gender, a higher CpG1 methylation level was also identified in EH in both males (p = 0.034) and females (p = 0.020). Receiver operating characteristic curves showed that CpG1 methylation was a significant predictor of EH. Furthermore, CpG1 methylation was inversely correlated with uric acid levels in controls. The present study suggests that CpG1 hypomethylation in the AGTR1 promoter is likely associated with the risk of EH in the population assessed. (C) 2015 S. Karger AG, Basel
引用
收藏
页码:95 / 102
页数:8
相关论文
共 39 条
[1]   Association between blood pressure and DNA methylation of retrotransposons and pro-inflammatory genes [J].
Alexeeff, Stacey E. ;
Baccarelli, Andrea A. ;
Halonen, Jaana ;
Coull, Brent A. ;
Wright, Robert O. ;
Tarantini, Letizia ;
Bollati, Valentina ;
Sparrow, David ;
Vokonas, Pantel ;
Schwartz, Joel .
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2013, 42 (01) :270-280
[2]  
Bassil CF, 2013, METHODS MOL BIOL, V1049, P95, DOI 10.1007/978-1-62703-547-7_9
[3]   Epigenetic modification of the renin-angiotensin system in the fetal programming of hypertension [J].
Bogdarina, Irina ;
Welham, Simon ;
King, Peter J. ;
Burns, Shamus P. ;
Clark, Adrian J. L. .
CIRCULATION RESEARCH, 2007, 100 (04) :520-526
[4]   Glucocorticoid Effects on the Programming of AT1b Angiotensin Receptor Gene Methylation and Expression in the Rat [J].
Bogdarina, Irina ;
Haase, Andrea ;
Langley-Evans, Simon ;
Clark, Adrian J. L. .
PLOS ONE, 2010, 5 (02)
[5]   Characterization of the angiotensin (AT1b) receptor promoter and its regulation by glucocorticoids [J].
Bogdarina, Irina G. ;
King, Peter J. ;
Clark, Adrian J. L. .
JOURNAL OF MOLECULAR ENDOCRINOLOGY, 2009, 43 (1-2) :73-80
[6]   Tobacco-Smoking-Related Differential DNA Methylation: 27K Discovery and Replication [J].
Breitling, Lutz P. ;
Yang, Rongxi ;
Korn, Bernhard ;
Burwinkel, Barbara ;
Brenner, Hermann .
AMERICAN JOURNAL OF HUMAN GENETICS, 2011, 88 (04) :450-457
[7]   Aging and Environmental Exposures Alter Tissue-Specific DNA Methylation Dependent upon CpG Island Context [J].
Christensen, Brock C. ;
Houseman, E. Andres ;
Marsit, Carmen J. ;
Zheng, Shichun ;
Wrensch, Margaret R. ;
Wiemels, Joseph L. ;
Nelson, Heather H. ;
Karagas, Margaret R. ;
Padbury, James F. ;
Bueno, Raphael ;
Sugarbaker, David J. ;
Yeh, Ru-Fang ;
Wiencke, John K. ;
Kelsey, Karl T. .
PLOS GENETICS, 2009, 5 (08)
[8]  
CLARK SJ, 1994, NUCLEIC ACIDS RES, V22, P2990, DOI 10.1093/nar/22.15.2990
[9]   CpG islands and the regulation of transcription [J].
Deaton, Aimee M. ;
Bird, Adrian .
GENES & DEVELOPMENT, 2011, 25 (10) :1010-1022
[10]   Aberrant methylation of the GCK gene body is associated with the risk of essential hypertension [J].
Fan, Rui ;
Wang, Wei-Jie ;
Zhong, Qi-Long ;
Duan, Shi-Wei ;
Xu, Xu-Ting ;
Hao, Ling-Mei ;
Zhao, Jing ;
Zhang, Li-Na .
MOLECULAR MEDICINE REPORTS, 2015, 12 (02) :2390-2394