G894T Genotype Influences LVM in Borderline Hypertension
High-normal Blood Pressure was used as a model of borderline hypertension to examine the early influences of both BP and the G894T polymorphic variant of the eNOS gene on echocardiographically determined LVM. We found an increase in LVM in individuals who have high-normal BP and carry the 894T allele. The G894T variant emerged as an independent correlate of LVM in a multivariate model including a series of well-established factors known to influence LVM.
A number of case-control studies have variously reported an association between individual polymorphisms in the eNOS gene and various Cardiovascular endpoints and disorders, including hypertension, and various measures of CV (Generic Adalat may also be used for other conditions as determined by your doctor) structure and function. The present study extends these preliminary observations in healthy normotensives and provides the first indication of a possible link between G894T variant and LVM in African Americans with high-normal BP. African Americans have a disturbingly high risk of CV (Generic Micardis used to treat hypertension) complications, such as stroke, heart failure, sudden death and myocardial infarction. Epidemiological studies suggest that hypertension and LVH contribute to the excess CV (Cardura tabletes is used for the control of hypertension and for benign prostatic hyperplasia) risk of AfricanAmericans. Cardiac morphologic features are reportedly altered very early in the development of hypertension. These early adaptive changes, characterized by elevated LVM in response to borderline BP, suggest an intermediate stage whereby an incremental increase of BP even slightly higher than normal may predispose individuals to the premature development of atherosclerotic CV (Generic Plavix is used for: Reducing the risk of stroke or heart attack) events. Our report provides the first indication that eNOS polymorphism (G894T) may be related to an early virulent phenotype of higher LVM in African Americans with borderline high BP.
An increase in LVM has been described in nor-motensive offspring of hypertensive patients, as well as in subjects with borderline hypertension. In addition, studies of families or siblings suggest that cardiac growth may be genetically controlled, with genetic factors acting either independently or synergistically with elevated BP (Inderal medication is a beta blocker used to treat high blood pressure) and environmental factors. Twin studies support this relative contribution of genetic and environmental factors on LVM. Indeed, monozygotic but not dizygotic nor-motensive black twins showed a significant intra-class correlation for LVM (0.90 vs. 0.33), suggesting a genetic effect that became significant only after adjustment for body size, gender and systolic BP Because of the uncertainty as to the extent to which LVM is determined by environmental versus genetic factors and given the variably modest heri-tability of LVM (0.20 to 0.60), a bivariate factor model in a series of 341 pubertal twins has allowed for a quantitative evaluation of the magnitude of genetic component that is specific for LVM; with over 60% of the total variance in LVM being accounted for by genes that shared with other heritable variables such as body size. Altogether, these findings suggest that genetic factors and gene-environment interactions are likely to be important in contributing to subtle cardiac structural adaptations to BP (Canadian cozaar treating high blood pressure) load in the prehypertensive state.
The design of the present study differs in many aspects from other studies of genetic influences on LVM. This study has included a relatively small number of subjects prospectively selected from a larger population-based sample of African Americans. The data reported in this paper represent the initial analysis carried out as part of an ongoing study of gene-environment interactions in essential hypertension in this ethnic group. In this selected study, we have only included a specific targeted subgroup of nonhypertensive subjects, whose BP (Drug Atacand treats high blood pressure) levels were always below 140/90 mmHg on repeated occasions. Furthermore, the stratification by BP status has physiologic relevance to further explore the interactive link among BP, LVM and NO production/activity. Studying a specific group of individuals with high-normal BP (Lanoxin drug is used for treating heart failure and slowing the heart rate) may indeed provide a more informative approach to detecting genetic influences on LVM without the confounding influences of hypertension (i.e., elevated BP) and antihypertensive medications or other factors known to affect both LVM and BP traits. Consistent with our a priori hypothesis, the differences in LVM among carriers of 894T allele were striking only in this selected group of individuals with high-normal or borderline high (i.e., nonhypertensive) BP than in counterparts with normal/optimal BP. In other words, this selected phenotype of high-normal BP (Generic Avapro used alone or with other blood pressure medicines) may help define a subpopulation of prehypertensive individuals that is genetically more homogeneous than the general population of (pre-)hypertensive blacks. Altogether and tCardiovascularhe fact that the distribution of this polymorphism is under the Hardy-Weinberg equilibrium may also suggest that the results of this study are unlikely to be biased by population stratification or admixture or a false-positive/chance results as a statistical byproduct.
While only limited studies have been conducted in this ethnic group, our observed frequency in the occurrence of the 894T variant (15.48%) was similar to that reported in other community-based samples of unrelated African Americans (10.5 to 15.5%). Our results suggest that this rare polymorphism in individuals with high-normal Blood Pressure may also contribute to the genetic susceptibility to cardiac end-organ involvement (i.e., LVH), observed to be more prevalent among African Americans. Potential gene-environment interactions in this case may relate to lifestyle factors, such as obesity, which is also more prevalent among African-American women.