Genotyping of CA Microsatellite in the HSD11B2 Gene and its Association with Cortisol to Cortisone Ratio in Chilean Hypertensive Children

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-743
Carolina Valdivia*1, Cristian A Carvajal1, Carmen Campino1, Carlos F Lagos1, Andrea Vecchiola1, Fidel Allende1, Sandra Solari1, Alejandro Martínez-Aguayo2, Marlene Aglony1, Rodrigo Bancalari1, Alejandra Tapia1, Cristobal A Fuentes1, Rene Baudrand1, Gareth Ivor Owen1, Hernan Garcia Bruce1 and Carlos E Fardella1
1Pontificia Universidad Catolica de Chile, Santiago, Chile, 2Pontificia Universidad Católica de Chile, Santiago, Chile
Recently we reported that 15% of Chilean adults hypertensive having an impairment in HSD11B2 gene expression (1). A low expression of this gene has been associated with an inappropriate activation of MR by cortisol. The length of cytosine-adenine (CA) microsatellite located in intron 1 of HSD11B2 gene (CA-M), has been associated to changes in cortisol to cortisone ratio (F/E) (2), but this has not been evaluated in children. 

Aim To study the early impact of the CA-M length in the F/E and the blood pressure (BP) in a pediatric cohort. 

Subjects and Methods Children (n=198) was classified in 82 hypertensives (H), 49 normotensives with hypertensive parents (NH) and 68 normotensives with normotensives parents (NN) (4-15 years old). We measured clinical (sdsBMI, blood pressure index (BPi)) and biochemical variables (F/E, as indicator of the 11beta-HSD2 activity). Genomic DNA was isolated from PBMC to amplify by PCR the region containing the CA-M, the PCR product was measured by DNA fragment analysis (in ABI3730XLs). The alleles length has been dicotomized in < 21 repeat of CA (short) or ≥ 21 CA alleles (long).We classified the subjects in 3 groups by alleles length: both shorts (SS); one short and other long (SL) and both long (LL). The results were expressed as median [Q1-Q3] and compared by Kruskal-Wallis, Mann Withney or Spearman test by Prism v5.0. 

Results Serum F/E was higher in H group than in normotensive group (NN+NH) (2.95[2.48-4.09] vs. 2.77[2.19-3.42] p=0.025). A higher sdsBMI was found in H than normotensive group (1.73[1.00-2.14]; 1.04[0.18-1.54] p<0.0001). The genotypic frequency for CA-M was no different between H, NH and NN groups (n=198, X2=0.68, df=4, p=0.68). We also classified subjects according the length of the CA-M in 3 groups: SS (n=87), SL (n=94) and LL (n=17)). In these groups, we did not find any differences in: F/E (2.9 [2.2-3.6]; 2.9[2.3-3.5]; 2.6[2.3-4.6] p NS), sdsBMI (1.21[0.24-1.81]; 1.33[0.57-1.83];  1.47[0.02-2.16] p NS), SBPi (1.1[1.0-1.2]; 1.1[1.0-1.2]; 1.2[1.0-1.3] p NS) and (DBPi 1.1[1.0-1.2]; 1.1[1.0-1.2]; 1.2[1.1-1.3] p NS). However, there is a positive correlation between F/E and SBPi (n=198, Spearman r= 0.267, p=0.0001). 

Conclusion In contrast with our previous studies performed in adults, these results shows that in children the lengths of CA-M have no effect in F/E and BP. However, the positive association of F/E with SBPi, suggest that other mechanisms related to HSD11B2 gene expression could lead to hypertension.

(1) Campino, C et al. Endocrine  2010; 37(1), 106–14. (2) Carvajal, C et al. Journal of hypertension 2005, 23(1), 71–7.

Nothing to Disclose: CV, CAC, CC, CFL, AV, FA, SS, AM, MA, RB, AT, CAF, RB, GIO, HG, CEF

*Please take note of The Endocrine Society's News Embargo Policy at

Sources of Research Support: Supported by Chilean grants: 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).