The 894T allele of the endothelial nitric oxide synthase gene is related to left ventricular mass in African Americans with high-normal blood pressure

Abstract

Background and Objectives: The 894T allele in exon 7 of the endothelial nitric oxide synthase (eNOS) gene has been inconsistently associated with hypertension in different racial groups. Because high-normal blood pressure (BP) confers an increased risk for the development of hypertension and other cardiovascular disorders, including left ventricular hypertrophy (LVH), we tested the hypothesis that the allelic variation (894T) in the eNOS gene would directly correlate with alterations in LV mass (LVM) in individuals with high-normal BP.Methods: Genotype distrbution of G894T was compared between 20 African Americans (10 females/1O males) with highnormal BP (systolic BP of 130-139 and/or diastolic BP of 85-89 mmHg) and 64 counterparts (37 females/27 males) with normal BP (<130/85 mmHg). Echocardiographic LVM was calculated (Devereux formula) and indexed to body surface area to define the presence of LVH (LVMI >134/1 10 g/m2 for men/women). Results: For the entire group, the 894T allelic frequencies (15,48%) and G894T genotype distributions were consistentwith the Hardy-Weinberg equilibrium expectations (estimated disequilibrium coefficient=0.01 18, P=0.40). LVMI was significantly higher in homozygous carriers (TT) of the rare 894T allele (n=3 females/0 males) than in heterozygous GT (n=1 3 females/7 males) and individuals bearing the GG (n=34 females/27 males) variant (124 ± 70 vs. 82 ± 24 and 82 ± 19 g/m2, respectively, P<0.05). The observed relationship between eNOS 894T allele and LVMI was restricted to individuals with high-normal BP (r=0.94, P=0.03) but not in those with normal BP (r=0.39, P=0.64), by analysis of variance (ANOVA) after adjusting for age, gender, body mass index, smoking and systolic BP. Conclusion: These findings, not previously described, provide important preliminary evidence to suggest an increased susceptibility to LVH in African Americans who carry the 894T variant of the eNOS gene and have high-normal blood pressure.

Association of Clinical and Genetic Factors With Left Ventricle Hypertrophy in Arterial Hypertension

“…It was found out that the A allele associated with higher prevalence of LVH [25], however not all the works confirmed this [26][27][28]. In our study the A allele prevalence was significantly lower in HT patients with LVH compared to the control group (23% vs 30%, p=0,047).…”

“…Полиморфизм Glu298Asp гена eNOS изучался по его влиянию на формирование ГЛЖ при АГ, и было выявлено, что аллель А ассоциируется с большей частотой ГЛЖ [25], однако это подтверждено не во всех работах [26][27][28]. В нашем исследовании А аллель гена eNOS достоверно реже встречался в группе больных АГ с ГЛЖ по сравне-нию с группой контроля (23% против 30%, р=0,047).…”

Prevalence and Correlates of Left Ventricular Hypertrophy in the African American Study of Kidney Disease Cohort Study

“…Recently identified candidate genes that are more common in African Americans and also seem to be associated with higher LVM or inappropriate LVH include a variant of the corin gene, 49 a polymorphism in the calcineurin gene, 50 and the 894T allele of endothelial NO synthase gene. 51 The high prevalence of LVH in this population raises the question of whether LVH itself should be a therapeutic target. Regression of LVM with effective BP reduction has been demonstrated in Ͼ400 clinical studies, but Ͻ10% have been double-blind, placebo-controlled studies.…”

Association between 894G>T endothelial nitric oxide synthase gene polymorphisms and metabolic syndrome

“…A common variation of the NOS3 that leads to an amino acid substitution in the mature protein is the 894G>T or Glu298Asp variant, in which a guanine/thymine substitution at exon 7 leads to a glutamate/aspartate substitution at position 298 (14). This variant has been associated with CAD (12,15), including an investigation in Brazilian subjects (16,17).…”