Left ventricular structure and function in relation to steroid biosynthesis genes in a white population

Yu Jin, Tatiana Kuznetsova, Lorena Citterio, Lutgarde Thijs, Elisabetta Messaggio, Nunzia Casamassima, Paolo Manunta, Robert Fagard, Giuseppe Bianchi, Jan A. Staessen

Research output: Contribution to journalArticle

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Abstract

Background Both 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. GAAA). 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.

Original languageEnglish
Pages (from-to)986-993
Number of pages8
JournalAmerican Journal of Hypertension
Volume25
Issue number9
DOIs
Publication statusPublished - Sep 2012

Fingerprint

Cholesterol Side-Chain Cleavage Enzyme
Left Ventricular Function
Steroids
Haplotypes
Population
Genes
Ventricular Remodeling
Ouabain
Aldosterone
Single Nucleotide Polymorphism
3-Hydroxysteroid Dehydrogenases
Left Ventricular Hypertrophy
Echocardiography
Genotype
Hormones
Enzymes

Keywords

  • blood pressure
  • epidemiology
  • genetic association study
  • hypertension
  • left ventricle
  • steroid hormone biosynthesis

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Jin, Y., Kuznetsova, T., Citterio, L., Thijs, L., Messaggio, E., Casamassima, N., ... Staessen, J. A. (2012). Left ventricular structure and function in relation to steroid biosynthesis genes in a white population. American Journal of Hypertension, 25(9), 986-993. https://doi.org/10.1038/ajh.2012.69

Left ventricular structure and function in relation to steroid biosynthesis genes in a white population. / Jin, Yu; Kuznetsova, Tatiana; Citterio, Lorena; Thijs, Lutgarde; Messaggio, Elisabetta; Casamassima, Nunzia; Manunta, Paolo; Fagard, Robert; Bianchi, Giuseppe; Staessen, Jan A.

In: American Journal of Hypertension, Vol. 25, No. 9, 09.2012, p. 986-993.

Research output: Contribution to journalArticle

Jin, Y, Kuznetsova, T, Citterio, L, Thijs, L, Messaggio, E, Casamassima, N, Manunta, P, Fagard, R, Bianchi, G & Staessen, JA 2012, 'Left ventricular structure and function in relation to steroid biosynthesis genes in a white population', American Journal of Hypertension, vol. 25, no. 9, pp. 986-993. https://doi.org/10.1038/ajh.2012.69
Jin, Yu ; Kuznetsova, Tatiana ; Citterio, Lorena ; Thijs, Lutgarde ; Messaggio, Elisabetta ; Casamassima, Nunzia ; Manunta, Paolo ; Fagard, Robert ; Bianchi, Giuseppe ; Staessen, Jan A. / Left ventricular structure and function in relation to steroid biosynthesis genes in a white population. In: American Journal of Hypertension. 2012 ; Vol. 25, No. 9. pp. 986-993.
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AU - Jin, Yu

AU - Kuznetsova, Tatiana

AU - Citterio, Lorena

AU - Thijs, Lutgarde

AU - Messaggio, Elisabetta

AU - Casamassima, Nunzia

AU - Manunta, Paolo

AU - Fagard, Robert

AU - Bianchi, Giuseppe

AU - Staessen, Jan A.

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N2 - Background Both 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. GAAA). 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.

AB - Background Both 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. GAAA). 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.

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