Association between aldosterone synthase (CYP11B2) polymorphism and left ventricular mass in human essential hypertension

Stella, Paola; Bigatti, Giada; Tizzoni, Laura; Barlassina, Cristina; Lanzani, Chiara; Bianchi, Giuseppe; Cusi, Daniele

doi:10.1016/j.jacc.2003.08.034

Cited by 53 publications

(60 citation statements)

References 26 publications

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“…However, the association between polymorphisms in the CYP11B2 gene and hypertension is controversial. [7][8][9][10][11][12][13][14][15][16][17][18][19] In the present study, we performed extensive association studies between polymorphisms in CYP11B2 regions and renin-aldosterone profiles and blood pressure values. Our findings in study population II indicate that subjects with the TT genotype of the T(Ϫ344)C polymorphism appear to have higher aldosterone levels in response to PRA levels than those with the TC or CC genotype when renin activity is Ͻ2.45 (e 0.9 ϭ2.45; Figure 2).…”

Section: Discussionmentioning

confidence: 99%

“…The T(Ϫ344)C polymorphism, which is located at the putative binding site for the steroidogenic transcriptional factor, has been reported to be associated with hypertension [7][8][9][10][11][12] and/or hypertension-related phenotypes, such as the plasma aldosterone level, 12,13 urinary aldosterone excretion, 8,14 aldosterone:renin ratio, 7,11,12,[15][16][17] and left ventricular hypertrophy. 18 We reported previously that the T(Ϫ344)C polymorphism was unlikely to influence the blood pressure status in the Japanese population based on an analysis of 4049 subjects recruited from the Suita Study.…”

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confidence: 99%

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Polymorphism of CYP11B2 Determines Salt Sensitivity in Japanese

et al. 2007

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Abstract-Aldosterone plays essential roles in body fluid and electrolyte homeostasis and blood pressure. However, the association between polymorphisms in the CYP11B2 gene and hypertension is controversial. We resequenced CYP11B1 and CYP11B2 and identified 35 polymorphisms in this region. We performed association studies between the plasma aldosterone concentration and 13 polymorphisms in this region in 1443 subjects. The subjects were all obtained from the Suita Cohort Study. Multiple regression analysis indicated that aldosterone levels were determined by renin activity, age, total cholesterol, and hematocrit. Residuals of the aldosterone levels after adjusting for these confounding factors were nominally associated with the T(Ϫ344)C (Pϭ0.0026), C(595)T (Pϭ0.0180), Ϫ(4837)C (Pϭ0.0310), and G(4936)A (Pϭ0.0498) polymorphisms. Only the T(Ϫ344)C polymorphism was significantly associated with the aldosterone level after a correction for multiple testing (Bonferroni). A significant interaction was observed between the T(Ϫ344)C polymorphism and renin activity in determining aldosterone levels. Moreover, a significant interaction was observed in 2063 subjects between urinary sodium excretion, which reflects sodium intake, and the T(Ϫ344)C polymorphism in determining systolic blood pressure. Only subjects with the TT genotype showed a positive correlation between urinary sodium excretion and systolic blood pressure. In vitro experiments confirmed the functional significance of this T(Ϫ344)C polymorphism in terms of angiotensin II reactivity. Thus, the T(Ϫ344)C polymorphism in CYP11B2 appears to affect salt sensitivity in Japanese and to have clinical significance.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Polymorphism of CYP11B2 Determines Salt Sensitivity in Japanese

et al. 2007

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“…In the n > 200 EH subgroup (Isaji, 28 Stella 27 ), CC had larger LVESD than TT (p heterogeneity = 0.15, p value < 0.0001, 95% CI −1.02 (−1.45, −0.60)). Under the C/T allelic model, the C allele had larger LVESD values than the T allele in the EH subset 8,27 (I 2 = 0, p heterogeneity = 0.39, p value < 0.0001, 95% CI −0.72 (−0.97, −0.47)).…”

Section: Lvesdmentioning

confidence: 99%

“…When removing the major case of heterogeneity (Olcay 30 ) from the EH group, the results showed that CC had larger LVEDD values than TT (p heterogeneity = 0.96, I 2 = 0%, 95% CI -0.86 (−1.14, −0.59), p value < 0.0001). Under the C/T allelic model, the C allele had larger LVEDD than the T allele in the EH subset 8,27 (I 2 = 0, p heterogeneity = 0.7, p value < 0.0001, 95% CI −0.54 (−0.79, −0.30)).…”

Section: Lveddmentioning

confidence: 99%

Association of echocardiographic left ventricular structure and −344C/T aldosterone synthase gene variant: A meta-analysis

Wang

Zhou

Zhang

et al. 2014

J Renin Angiotensin Aldosterone Syst

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Background: Aldosterone synthase (CYP11B2) is one of the most studied candidate genes related to essential hypertension (EH) and left ventricular hypertrophy (LVH). Some studies have focused on the relationship between −344C/T polymorphism (rs1799998) in the CYP11B2 gene and LVH, but the results are controversial. This meta-analysis is purposed to reveal the relationship between the −344C/T and the left ventricular structure and function, including left ventricular end diastolic dimension (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular mass/left ventricular mass index (LVM/LVMI), left ventricular posterior wall thickness (LVPWT), and interventricular septal wall thickness (IVS). Methods: A literature search of PubMed and Embase databases was conducted on articles published before January 27, 2014. The odds ratios with 95% confidence intervals were calculated. Heterogeneity analyses were performed using meta-regression. Tests for publication bias were also performed and biased studies should be removed from subsequent analyses. Results: There were 20 studies with a total of 6780 subjects meeting the inclusion criteria. The main finding was that concentration levels of LVEDD and LVESD were higher in CC homozygous individuals than in TT homozygous individuals in the whole group. In the Asian subgroup, TT homozygous individuals had larger IVS than CC homozygous individuals. In the Caucasian normotension subgroup, CC homozygous individuals had larger LVM/LVMI than TT homozygous individuals. In the Asian essential hypertension subgroup, TT homozygous individuals had larger LVPWT values than CC homozygous individuals. Conclusions: The present findings support the hypothesis that CC homozygous individuals may have greater left ventricular diameters (LVEDD and LVESD) regardless of their ethnicities or physical conditions.

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“…16 High serum aldosterone can result in hypertrophy of myocardial cells. [17][18][19] In humans, aldosterone synthase is encoded by the CYP11B2 gene. The C-344T variant in the regulatory region of the CYP11B2 gene was associated with enhanced aldosterone production.…”

Section: Discussionmentioning

confidence: 99%

The relationship between left ventricular hypervoltage and CYP11B2 (344T/C) polymorphism in Keriyans

Cao

Qiu

Zhu

et al. 2011

J Renin Angiotensin Aldosterone Syst

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Introduction: The 'desert people' or Keriyans are able to maintain normal body functions whilst living in the hot, arid areas of Taklimakan Desert. However, little is known about the adaptive mechanisms in this extreme environment. We explored the relationship between polymorphism of C-344T in the promoter region of the aldosterone synthase gene (CYP11B2) and resting electrocardiogram (ECG) hypervoltage in this population. Materials and methods:The study recruited 503 Keriyans who were living in the Taklimakan Desert and 237 age/gendermatched controls from the Uighurs living in neighbouring villages. Parameters of physical fitness, ECGs, and biochemistry were compared between the two groups. The C-344T single nucleotide polymorphism (SNP) in the promoter region of CYP11B2 was genotyped by polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) and sequencing. Results: The incidence of ECG left ventricular hypervoltage in the Keriyans was significantly higher than that in the controls (p < 0.001). The frequency of allele 344T was higher in this population than that in the controls (OR = 1.48; 95% CI:1.082-2.023). A higher OR for allele 344T was also seen in Keriyans with ECG left ventricular hypervoltage against those without this finding (OR = 1.557; 95% CI:1.032-2.349). Conclusion:The polymorphism of C-344T in the promoter region of the CYP11B2 gene was associated with ECG left ventricular hypervoltage in the Keriyan population.

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Association between aldosterone synthase (CYP11B2) polymorphism and left ventricular mass in human essential hypertension

Abstract: Our data suggest that -344C/T polymorphism affects LV mass and thickness in essential hypertension, independent of adrenal aldosterone. A role for intracardiac aldosterone synthesis is hypothesized.

Cited by 53 publications

References 26 publications

Polymorphism of CYP11B2 Determines Salt Sensitivity in Japanese

Polymorphism of CYP11B2 Determines Salt Sensitivity in Japanese

Association of echocardiographic left ventricular structure and −344C/T aldosterone synthase gene variant: A meta-analysis

The relationship between left ventricular hypervoltage and CYP11B2 (344T/C) polymorphism in Keriyans

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