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ACE and AGTR1 are differentially methylated in a hypertensive versus normotensive cohort of Kenyans
Author(s) -
Shelton Dimond A.,
Rice Nancy A.
Publication year - 2018
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.2018.32.1_supplement.787.20
Subject(s) - dna methylation , cpg site , methylation , epigenetics , endocrinology , medicine , promoter , biology , angiotensin ii , bisulfite sequencing , gene , genetics , blood pressure , microbiology and biotechnology , gene expression
Cardiovascular diseases (CVD) are emerging as the primary cause of global mortality and are disproportionately affecting low and middle‐income countries (LMICs). The leading risk factor for CVD is hypertension (HTN), a multifactorial disease with no single genetic cause. Epigenetic control, i.e. methylation, of blood pressure regulatory genes likely contributes to the etiology of this disease. From a rural population of Kenyans previously identified to have a high incidence of HTN, we investigated the cytosine‐phosphate‐guanine dinucleotide (CpG) methylation pattern of two promoter regions that regulate renin‐angiotensin aldosterone system (RAAS) gene expression. Specifically, angiotensin II receptor type 1 ( AGTR 1 ) and angiotensin‐converting enzyme ( ACE ) genes, that function in maintaining salt and water homeostasis, were analyzed. The promoter regions of AGTR‐ 1 and ACE contain 11 and 19 CpG islands, respectively, making them a prime target for methylation driven regulation. Briefly, genomic DNA was isolated from buccal cells isolated from either hypertensive or normotensive individuals using standard alkaline lysis. DNA was quantified, and subsequently unmethylated cytosines were converted to uracils by demethylation using bisulfite treatment. Gene‐specific CpG islands were amplified by PCR and sequenced. From preliminary results, ACE promoter methylation is increased by 10 % (50.4 ± 3 vs 60.1 ± 4; p <0.05) and AGTR 1 promoter methylation is decreased by 8 % (61.0 ± 8.2 vs 53.8 ± 4.0; p, 0.05) in hypertensive individuals versus normotensive, respectively. Specifically, the 18 th CpG dinucleotide in ACE was unmethylated in all samples isolated from normotensive or prehypertensive individuals, yet was methylated in the majority of samples isolated from participants with elevated blood pressure. These results may suggest a role for this dinucleotide in regulating ACE gene expression in endothelial dysfunction. Support or Funding Information This work was funded by NIH‐NCRR P20 RR16481 (NAR) as well as support from the Kentucky Academy of Sciences (NAR). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .