CPG METHYLATION IN 11BETA-HYDROXYSTEROID DEHYDROGENASE TYPE2 PROMOTER IS INCREASED IN ADULT ESENTIAL HYPERTENSIVES

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 723-757-Renin-Angiotensin-Aldosterone System/Endocrine Hypertension
Bench to Bedside
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-741
Cristian A Carvajal*1, Simonetta Friso2, Alejandra Tapia1, Silvia Udali2, Carolina Valdivia1, Carmen Campino1, Carlos F Lagos1, Hernan García1, Marlene Aglony1, Andrea Vecchiola1, Cristobal A Fuentes1, Oliviero Olivieri2 and Carlos E Fardella1
1Pontificia Universidad Catolica de Chile, Santiago, Chile, 2University of Verona School of Medicine, Verona, Italy
We reported that 15% of essential hypertensives might suffer from impairment of the enzyme 11beta-hydroxysteroid-dehydrogenase type 2 (11BHSD2). 11BHSD2 activity and expression can be affected by mutations, polymorphisms, and lately, epigenetic modifications. Aim: To evaluate the HSD11B2 promoter methylation, cortisol to cortisone (F/E) ratio and HSD2 expression in adults and pediatric essential hypertensives (HT). Subjects and Methods: We recruited 64 patients, grouped in 16 HT and 16 Normotensive (NT) adults; 16 HT and 16 NT pediatrics. We measured serum aldosterone, plasma renin activity (PRA), cortisol (F) and cortisone (E). PBMC bisulfite–treated DNA was used to perform the methylation-specific PCR (MS-PCR) and calculated the methylation index in HSD11B2 promoter (region -200 to -400 bp; NG_001087). In a subgroup of HT patients (n=10) we also evaluated the HSD2 and U6 (housekeeping) expression in PBMC by RT-PCR and further associated with CpG methylation in HSD11B2 promoter Data are expressed as mean±SD. Statistical comparisons were performed by Kruskal-Wallis with Dunn's Multiple Test with Prism v5.0 software. Results: HT adults have higher methylation index compared with NT adults (0.154±0.031 vs. 0.072±0.011, p<0.05) that HT and NT children have low and similar methylation (0.021±0.005 vs. 0.052±0.008, p NS). Interesting, HT adults had higher serum F/E ratio than NT and higher than either HT or NT children (4.1±1.1 vs. 2.8±0.6 and 3.3±0.8 vs. 2.8±1.1, Anova p<0.001). In PBMC, we found a trend to low expression of HSD2 in patients with higher methylation index in HSD11B2 promoter (r=0.65; p 0.11).Conclusions: CpG methylation of HSD11B2 promoter is increased in adult essential hypertensives compared to NT adults and either HT/NT children. A high F/E ratio is in agreement with a low activity of renal HSD11B2 previously reported. Preliminary studies support that HSD11B2 methylation index in PBMC as potential molecular biomarker of mineralocorticoid activity and essential hypertension.

Nothing to Disclose: CAC, SF, AT, SU, CV, CC, CFL, HG, MA, AV, CAF, OO, CEF

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: FONDEF D08i1087, FONDEF IDeA CA12i10150, FONDECYT 1100356 & 1130427, SOCHED 2012-04 & IMII P09/016-F. CFL and CAC are PhD fellows from Comision Nacional y Cientifica de Chile (CONICYT). BECA APOYO CONICYT 24121639.