Faculty school or centre title here The involvement
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Faculty, school or centre title here The involvement of kidney DNA methylation in blood pressure regulation. Wise, I. A. , Tomaszewski, M. , Prestes, P. & Charchar, F. J.
Epigenetics of essential hypertension
Epigenetics HISTONE MODIFICATION DNA METHYLATION mi. RNAs 5’ 3’
DNA methylation at Cp. G islands Modifications Nucleosome DNA Methylation 5’ A C G T A T G T T A T C G A T T T C C G A T T C G 3’
Kidney methylation and blood pressure DNA methylation patterns are tissue specific. To date, there are no studies on DNA methylation patterns in the hypertensive kidney. Aim: To determine if loci specific DNA methylation is one of the mechanisms responsible for altered gene expression in the hypertensive kidney.
96 TRANSLATE study participants Clinical phenotyping 80 70 **** ** 60 50 40 ** 30 ** 20 10 0 Age, years (mean) Gender, % male Ever smoker, % Hypertensive Diabetes mellitus, % Normotensive BMI (mean)
Results Probe ID Gene Symbol CHR Location cg 14276698 OR 13 J 1 9 Open_sea cg 23409374 SLC 17 A 7 19 Island 8 S_Shelf cg 01451489 Description Olfactory & GPCRs signalling: Abnormalities related to high BP, cancer, inflammatory condition. Glutamate receptor signalling. cg 08337184 PRKCSH 19 N_Shore Advanced glycosylation endproduct receptor signalling. Losartan supressed RAGE activation. cg 03752425 ZFHX 3 16 Open_sea Circadian rhythm genes cg 02075570 SLC 45 A 3 1 Island Transport of glucose, sugars, bile salts, organic acids, metal ions and amine compounds. Associated with apo. B/apo. A 1. cg 02324221 C 10 orf 25 10 N_Shelf Open reading frame Adjustments: age, BMI, smoker status, diabetes, gender P<0. 0001
ZFHX 3 Located on chromosome 16, q 22. 3 Variants within this gene previously associated with coronary artery disease pathologies, including hypertension. Highly correlated to hypertension diagnosis (P = 4. 63 E-05) Cp. G site cg 03752425 hypermethylated, suggesting suppressed-expression of ZFHX 3 in the hypertensive kidney Adjustments: age, BMI, smoker status, diabetes, gender P<0. 0001
Conclusion & future research Methylation at site cg 03752425 correlated with hypertension diagnosis, suggesting possible mechanistic insight. Future research To investigate the relationship between methylation in the hypertensive kidney and gene expression variation.
Acknowledgements Nilesh, Artur Nathan, Uni Funding bodies Contact info
