Deletion Polymorphism of the Angiotensin I-Converting Enzyme Gene Is Associated with Increased Plasma Angiotensin-Converting Enzyme Activity but Not with Increased Risk for Myocardial Infarction and Coronary Artery Disease

Br, Winkelmann; Nauck, Markus; Klein, Bärbel; Ap, Russ; Bo, Böhm; Siekmeier, R.; Ihnken, Kai; Verho, M; Wl, Gross; März, Winfried

doi:10.7326/0003-4819-125-1-199607010-00004

Cited by 96 publications

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“…2,19 Other factors also influence the ACE level and these include exercise, diet and body weight. 4,20,21 Elevated ACE levels have been implicated in the pathogenesis of several disorders, 7,8,[19][20][21][22][23] though there are some contradictory reports. 7 In addition, the renin-angiotensin system is known to play an important role in metabolism and influence insulin action, thus affecting different metabolic pathways.…”

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confidence: 99%

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Increased Frequency of Angiotensin-Converting Enzyme DD Genotype in Saudi Overweight and Obese Patients

El‐Hazmi

Warsy

2003

Ann Saudi Med

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Background: Several studies have been carried out to investigate the insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) in obese and normal weight individuals, often with contradictory results in different populations. In some studies, the DD genotype occurs at a high frequency in obesity, while in others no association has been demonstrated. Since obesity and overweight are of frequent occurrence in the Saudi population, we initiated this study to investigate the I/D polymorphism of ACE in obese, overweight and normal weight Saudis. Patients and Methods:The study group included 457 Saudi males and females. The height and weight were measured and body mass index (BMI) was calculated. Based on the BMI value, the total study population was classified as normal, overweight and obese. A total of 117 obese (BMI>30 (kg/m 2 )), 185 overweight (BMI=25-29.9 (kg/m 2 )) and 155 normal weight individuals (BMI<(kg/m 2 )) were enrolled. Polymerase chain reaction (PCR) and agarose gel electrophoresis were used to study the ACE polymorphism. For the deletion (D) form, a 190 bp and for the insertion (I) form, 490 bp DNA fragment were obtained on 2% agarose gel electrophoresis. Results: The frequency of DD genotype was 76.9% in the obese, and 73.5% in the overweight individuals, compared to 19.66% and 24.86% of the ID genotype in the obese and overweight, respectively. Among the normal weight individuals, the frequency was significantly lower for DD and higher for the ID genotype, i.e., 58.7% for DD and 40% for ID. The allele frequencies in the obese were 0.867 and 0.133 for the D and I alleles, respectively. While in the overweight, the frequencies were 0.859 and 0.141 for these alleles, respectively, compared to 0.787 and 0.213 in the normal weight individuals. Conclusions:The DD genotype and D allele occur at a high frequency in Saudi overweight and obese individuals, and may have some role in fat accumulation by affecting metabolic pathways of fat, thus leading to the development of overweight and obesity. Ann Saudi Med 2003;23(1-2) Angiotensin-converting enzyme (ACE; Kinininase II; EC 3.4.15.1) is a dipeptidyl exopeptidase that cleave carboxyl terminal dipeptide of angiotensin I (A-1) to form the octapeptide angiotensin II (A-II) and inactivates the vasodilator bradykinin.1 Recently, the genes of components of the rennin-angiotensin system, namely angiotensinogen, ACE and angiotensin II receptors, have been described in the adipose tissues and the gene expression of angiotensinogen has been studied in adipose tissues of obese patients. [2][3][4] The human ACE gene is located in chromosome 17q23 and has 26 exons and exhibits polymorphism caused by either an insertion (I) or deletion (D) of a 287 base pair (bp) alu-type sequence within intron 16, thus resulting in three genotypes: DD, ID and II.2 Circulating ACE levels show extensive inter-individual variability, and are highly genetically determined. 5Serum levels vary in the different genotypes, where highest levels are reported in the DD and lowest...

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confidence: 99%

“…2,6,7 In addition, the activity of the renin-angiotensin system appears to be regulated by food intake, suggesting that it may be involved in development of obesity and obesity related hypertension. 4 The genotype of ACE DD is shown to be linked to different disorders, including obesity, hypertension, diabetes mellitus and renal disease.…”

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Increased Frequency of Angiotensin-Converting Enzyme DD Genotype in Saudi Overweight and Obese Patients

El‐Hazmi

Warsy

2003

Ann Saudi Med

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“…In our study we expect that the number of survival in both gender will be similar, but as we observed that the deviations (differences between observed and expected), were different. When we compare the survival rate among both gender at age group (60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74) in 1995 vs. (73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87) in 2008, we observed more survival among males comparing to females (p=0.003), this means that the rate of mortality was higher among females, and the rate of survival was higher among males (p=0.003). Indeed, in 2008 we expected to have 86 males alive but we were surprised to find 108 males alive, in contrary we expected to have more females alive (157), but we only found 135 alive at 2008.…”

Section: Follow Upmentioning

confidence: 99%

“…Most studies focused on an insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene as a marker for a functional polymorphism, which has been related to a variation in the plasma level of the enzyme [65], and ACE activity [69,71] in a codominant pattern.…”

Section: Angiotensin Converting Enzyme (Ace)mentioning

confidence: 99%

Human Longevity: Nature versus Nurture, Survival versus Mortality~!2010-04-29~!2010-06-30~!2010-08-31~!

Bowirrat¹

2010

TOALTMEDJ

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Numerous studies were published, investigating the associations of ApoE and ACE polymorphisms with longevity. In 1995, we conducted based cross-sectional study among 823 elderly Arab residents in Israel for studying the prevalence and genetics of dementia of Alzheimer's type (DAT). Epidemiological and genes results of (ApoE + ACE) were reported The ApoE frequency was the lowest in the world and no association was found between ACE and DAT. During 2008, we conducted a follow up study looking for survival and mortality rate among the same participants to endeavor if there is any relationship between genes and longevity. The total mortality rate among both genders after thirteen years was 66.34%, and the survival subjects of 88 years or older were 34 persons only out of the initial number 270 in 1995 (34/270 = 12.6%). We used the Chi-Square test to examine the null hypothesis (no difference between observed and expected results): When we compare the survival rate among both sexes in age group (60-74) in 1995 vs. age group (73-87) in 2008. We observed statistically significant high survival rate among males (p=0.003) comparing to females in the same age groups. In contrary, at advanced age, when we compare the survival rate in age group (75-85+) in 1995 vs. age group (88-98+) in 2008, we observed high and significant survival rate among females (p=0.033).Conclusion: High rate of mortality was observed among females in age groups (60-74) in1995 and age group (73-87) in 2008, and high rate of mortality at advanced age was observed among males at advanced age group (75-85+) in 1995 and age group (88-98+) in 2008. More females live longer than men and no association was found between ApoE, ACE genes and longevity, that seems that longevity is exceedingly dependent on other genes in addition to the environmental factors.

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“…5,7 These findings have been recurrently confirmed by several investigators in populations of various ethnic origins. [8][9][10][11][12][13] Thus, the ACE gene is viewed as a quantitative trait locus (QTL) that modulates circulating ACE levels, and the ACE*I/D dimorphism is a marker that is in linkage disequilibrium with functional variants located in the ACE gene. As transient increase of ACE levels has been reported to occur during adolescence, 4 we sought to determine: 1) whether the ACE*I/D dimorphism tracked with ACE levels in younger individuals as well; 2) how these associations compared to those observed in adults; and 3) what the variance of the phenomenon among both adult and younger subjects was.…”

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The Angiotensin-Converting Enzyme (ACE) Gene Insertion/Deletion Dimorphism Tracks with Higher Serum ACE Activities in Both Younger and Older Subjects

et al. 1998

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Background:The absence of a 287 base pair alu sequence in the ACE gene (D allele) is associated with higher ACE levels than its presence (I allele) in adults. We carried out a case-control study of the ACE*I/D dimorphism in relation to circulating ACE activities to evaluate associations between the two variables in adults, compared to younger (18 years or less) individuals. Materials and Methods: Genotypes of the ACE*I/D dimorphism were determined on DNA samples from a population of 164 random (unrelated) Emirate nationals, composed of two groups: 112 subjects above 18 years of age (range=20-77 years), and 52 subjects of 18 years or less (range=1-18), and analyzed for putative associations with serum ACE activities. ACE*I/D genotypes of the 164 individuals were determined by assays based on polymerase chain reaction. ACE activities were determined on serum samples of these subjects by colorimetric assays. Results: The D allele was associated with increased ACE values in both adult and younger individuals. Mean ACE activity levels associated with II, ID and DD genotypes, however, were 42%-61% higher in the 18 years and under group of subjects. The ACE*I/D marker accounted for 28% of the variance of the phenomenon determining ACE levels in adults, and for 30% among youngsters. Conclusion:The ACE*I/D dimorphism correlated strongly with circulating ACE activities in both adult and young Emirati subjects, and the corresponding mean ACE activities were significantly higher among the youngsters.

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Deletion Polymorphism of the Angiotensin I-Converting Enzyme Gene Is Associated with Increased Plasma Angiotensin-Converting Enzyme Activity but Not with Increased Risk for Myocardial Infarction and Coronary Artery Disease

Abstract: In an angiographically defined study sample, ACE I/D gene polymorphism was not associated with an increased risk for coronary artery disease or myocardial infarction, despite its effects on plasma ACE activity.

Cited by 96 publications

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Increased Frequency of Angiotensin-Converting Enzyme DD Genotype in Saudi Overweight and Obese Patients

Increased Frequency of Angiotensin-Converting Enzyme DD Genotype in Saudi Overweight and Obese Patients

Human Longevity: Nature versus Nurture, Survival versus Mortality~!2010-04-29~!2010-06-30~!2010-08-31~!

The Angiotensin-Converting Enzyme (ACE) Gene Insertion/Deletion Dimorphism Tracks with Higher Serum ACE Activities in Both Younger and Older Subjects

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