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Household Air Pollution Indicators and Epigenetic Changes in the Renin Angiotensin System Genes ACE and AGTR1
Author(s) -
Swann Sellers,
Beach Kayman,
Ehmke Sarah,
Rice Nancy A.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.06878
Subject(s) - dna methylation , epigenetics , blood pressure , cpg site , methylation , angiotensin ii , medicine , pyrosequencing , endocrinology , gene , biology , physiology , genetics , gene expression
Cardiovascular diseases (CVD) are the world’s leading cause of mortality and disproportionately affect individuals in low and middle income countries (LMICs). Hypertension (HTN) is a multifactorial disease that is the current leading cause of CVD. In this study, we investigated the epigenetic regulation of two key genes involved in regulation of blood pressure, angiotensin‐converting enzyme ( ACE ) and angiotensin II receptor type 1 ( AGTR1 ), from a cohort of Kenyans known to have both a high prevalence of HTN and exposure to household air pollution (HAP). Genomic DNA, isolated from saliva samples, was used to quantify methylation of cytosine‐phosphate guanine (CpG) islands in the promoter regions of ACE or AGTR1 by pyrosequencing following bisulfite conversion. In preliminary samples (n=29) analyses indicate that when stratified by blood pressure, both ACE and AGTR1 are hypomethylated in hypertensive versus normotensive individuals (1.43 ± 0.316 vs. 1.524 ± 0.35 and 2.841 ± 1.35 vs. 2.104 ± 0.591, respectively). However, specific CpG3 dinucleotide in the AGTR1 promoter showed a significant 3% increase of methylation (5.652 ± 3.069 vs 2.638 ± 0.734; p=0.028) in hypertensive versus normotensive individuals. In this preliminary work, no significant associations were found between methylation and indicators of HAP, although a strong positive correlation exists between CpG2 and CpG4 methylation in AGTR1 (R=0.990; p<0.001). Our findings indicate epigenetic regulation of AGTR1 may have a role in modulating high blood pressure incidence in rural LMICs where HAP is epidemic. Support or Funding Information We acknowledge funding form the University of South Alabama to N.A.R.