Title: Left ventricular structure and function in relation to steroid biosynthesis genes in a white population
Authors: Jin, Yu
Kuznetsova, Tatiana
Citterio, Lorena
Thijs, Lutgarde
Messaggio, Elisabetta
Casamassima, Nunzia
Manunta, Paolo
Fagard, Robert
Bianchi, Giuseppe
Staessen, Jan A # ×
Issue Date: Sep-2012
Publisher: Elsevier
Series Title: American Journal of Hypertension vol:25 issue:9 pages:986-993
Article number: 10.1038/ajh.2012.69
Abstract: BackgroundBoth endogenous ouabain (EO) and aldosterone are steroid hormones which might play a role in the pathogenesis of left ventricular (LV) hypertrophy and cardiac remodeling. Cholesterol side-chain cleavage enzyme (CYP11A1) and 3β-hydroxysteroid dehydrogenase (HSD3B1) are two key enzymes in the pathway of steroid biosynthesis.MethodsWe investigated in 532 individuals (mean age, 50.3 years; 51.5% women) randomly recruited from a white European population whether LV structure and function were related to genetic variations in CYP11A1 and HSD3B1. We measured LV structure by conventional echocardiography and LV diastolic function by Doppler imaging of the transmitral blood flow and the mitral annular movement. We genotyped tag single nucleotide polymorphisms (SNPs) rs2279357, rs11638442 and rs2073475 in CYP11A1, and rs2236780, rs3765945, and rs6203 in HSD3B1.ResultsWhile adjusting for covariables and accounting for family clusters, LV mass index decreased (P ≤ 0.049) across the CYP11A1 genotypes in rs2279357 (CC vs. CT vs. TT), rs11638442 (GG vs. GC vs. CC), and rs2073475 (GG vs. GA+AA). Carriers of the CYP11A1 TCG haplotype had lower (P ≤ 0.017) LV mass and LV mass index than noncarriers. Carriers of HSD3B1 GCC haplotype had lower peak early (Ea; P = 0.004) and higher peak late (Aa; P = 0.066) diastolic mitral annular velocities and therefore a lower Ea/Aa ratio (P = 0.041) as compared with noncarriers. Neither plasma endogenous ouabain nor 24-h urinary aldosterone were related to any of the SNPs or haplotypes (P ≥ 0.07).ConclusionsPending confirmation in other studies, LV mass and LV diastolic function seem to be related to genetic variation in the steroid biosynthesis.American Journal of Hypertension 2012; doi:10.1038/ajh.2012.69.
ISSN: 0895-7061
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Hypertension and Cardiovascular Epidemiology
× corresponding author
# (joint) last author

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