The angiotensin I converting enzyme gene and predisposition to high blood pressure.

Abstract

Phenotypic abnormalities of the renin-angiotensin system have been associated with the predisposition to high blood pressure. The angiotensin I converting enzyme (ACE) gene has been implicated as a candidate gene. We examined the distribution of common alleles of the ACE gene and measured circulating components of the renin-angiotensin system and urinary sodium excretion in 170 young Caucasian adults with contrasting genetic predisposition to high blood pressure. Predisposition was defined on the basis of personal and parental blood pressure levels by using the four corners sampling method. Young adults with greatest predisposition who had high blood pressure and two parents with high blood pressure did not show any significant difference in the distribution of the markers of the ACE gene, either as genotype or allele frequencies, when compared with young adults with least predisposition who had low blood pressure and two parents with low blood pressure. Offspring with urinary sodium excretion above the median (143.4 mmol per day) also showed no significant differences in the distribution of ACE alleles or genotype between groups. Different genotypes were associated with different average serum ACE concentrations (p<0.0001), but plasma angiotensin II and aldosterone showed no significant variation with ACE genotype. These results suggest that in a group of Caucasians selected from the general population, the ACE gene is not associated with genetic predisposition to high blood pressure. In this population common ACE gene allelic markers would not be useful indexes of susceptibility to hypertension. (Hypertension 1993^21:455-460) KEYWORDS • blood pressure • angiotensin converting enzyme • genetics • family characteristics T he renin-angiotensin system has an important role in blood pressure homeostasis. We have shown in young adults with high blood pressure that plasma angiotensin II (Ang II) is higher when both parents have high blood pressure than when both parents have low blood pressure.1 The increase is associated with higher levels of plasma renin activity and angiotensinogen concentrations, 12 suggesting that genetic predisposition to high blood pressure may involve abnormalities of the renin-angiotensin system. A number of genes, including those coding for renin, angiotensinogen, and the angiotensin I converting enzyme (ACE), are possible candidates to explain the genetic basis of high blood pressure.

Association of a polymorphism at the 5′‐region of the angiotensin II type 1 receptor with hypertension

“…With respect to the ACE I\D polymorphism, the D allele displays a positive association with corresponding plasma ACE concentrations (Riget et al 1990 ;Tiret et al 1992 ;Morris et al 1994). Increases in ACE appear to result in increased Ang II formation in plasma, although this issue is still being debated (Harrap et al 1993 ;Ueda et al 1995). We suggest that increased Ang II formation, possibly combined with a higher number of receptors associated with the T allele of AT " , may lead to elevated blood pressure by synergism.…”

α-Adducin and Angiotensin I–Converting Enzyme Polymorphisms in Essential Hypertension

“…However, Schmidt et al, 25 studying Dutch parental couples who both had either high or low blood pressure and their offspring, found that allele frequencies were similar in parents with high and low blood pressure and in their offspring. Also, Harrap et al 26 could find no evidence that in a group of whites selected from the general population, the ACE gene was associated with genetic predisposition to high blood pressure. Interestingly, in Japanese patients with essential hypertension, the D allele was associated with early onset of hypertension and left ventricular hypertrophy, although blood pressure levels and the severity of damage to other organs were unaltered.…”

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

“…Various reports described the D allele as a risk factor for essential hypertension in various populations 6,7 whereas other studies disagree with that hypothesis. [8][9][10][11][12][13] Our work is, to our knowledge, the first one to be done in a Mediterranean population, and reveals no association between the I/D polymorphism and BP (Table 2). When we tested the serum activity of ACE in all of the individuals (fifth quintyl and first quintyl groups) it showed significantly higher values in individuals with more D alleles (DDϾDIϾII).…”

“…[1][2][3] The D allele was reported to be a risk factor for several cardiovascular diseases including myocardial infarction, left ventricular hypertrophy and essential hypertension in some populations under study, 4-7 but could not later be proven in others. [8][9][10][11][12][13] To our knowledge there is no evidence of any genetic study of ACE performed in a Mediterranean population.…”