Variation in the Region of the Angiotensin-Converting Enzyme Gene Influences Interindividual Differences in Blood Pressure Levels in Young White Males

Abstract

Background-The renin-angiotensin system regulates blood pressure through its effects on vascular tone, renal hemodynamics, and renal sodium and fluid balance. Methods and Results-Using data from a large population-based sample of 1488 siblings having a mean age of 14.8 years and belonging to the youngest generation of 583 randomly ascertained three-generation pedigrees from Rochester, Minn, we carried out variance components-based linkage analyses to evaluate the contribution of variation in four renin-angiotensin system gene regions (angiotensinogen, renin, angiotensin I-converting enzyme, and angiotensin II receptor type 1) to interindividual variation in systolic, diastolic, and mean arterial pressure. We rejected the null hypothesis that allelic variation in the region of the angiotensin-converting enzyme (ACE) gene does not contribute to interindividual blood pressure variability. After conditioning on measured covariates, variation in this region accounted for 0%, 13% (Pϭ0.04), and 16% (Pϭ0.04) of the interindividual variance in systolic, diastolic, and mean arterial pressures, respectively. These estimates were even greater in a subset of subjects with a positive family history of hypertension (0%, 29%

Angiotensin-converting enzyme (ACE) gene polymorphisms, serum ACE activity and blood pressure in a Spanish-Mediterranean population

“…16,17 Nevertheless, in our population the difference of genotype frequencies between men with highest BP (fifth quintyl) and men with lowest BP (first quintyl) was not significant (P = 0.468) ( Table 2), in agreement with a previous study. 18 We have not found a relationship between genotypes and family history of hypertension or evident clinical hypertension (data not shown).…”

Association of the angiotensin-converting enzyme (ACE) gene G2350A dimorphism with essential hypertension

“…Two large population-based studies found only marginally significant evidence of association and linkage, for BP and the I/D dimorphism. 12,16 Plasma ACE levels are remarkably stable within an individual, while marked differences are observed between individuals. 3,4 The results of a combined segregation-linkage analysis in French families suggested that the I/D dimorphism was in strong LD with an unmeasured functional mutation of the ACE gene.…”

“…Several studies on the association of ACE I/D dimorphism and the risk of developing CVDs, such as essential hypertension (EH) [9][10][11][12][13][14][15][16][17][18] and myocardial infarction (MI), [19][20][21][22][23][24][25][26][27][28] have generated inconsistent information. This instigated a search for new polymorphisms in the ACE gene to identify better markers or actual functional variants.…”

Relation between the angiotensin-converting enzyme insertion/deletion polymorphism and blood pressure in Japanese male subjects

“…17 Previously, we also reported that serum ACE levels were significantly higher in the DD and ID genotypes than in the II genotype in subjects who underwent cardiac catheterization 15 or renal biopsy 16 in our hospital. Recently, three studies, two in Caucasians 7,8 and one in Japanese, 9 independently reported a significant association between the ACE I/D polymorphism and hypertension in male subjects. The current study confirmed these earlier observations in our study population.…”

“…6 Several studies reported evidence of a significant relation between the ACE I/ D polymorphism and hypertension in male subjects but not in female subjects. [7][8][9] However, it was also shown that this relation was not consistently seen in male subjects, but was changeable depending on other factors such as age. 10 In addition, recent studies of population-based samples of three differ-ent areas in Japan presented conflicting results regarding the association of the ACE I/D polymorphism and hypertension.…”