Insertion/Deletion Polymorphism of the Angiotensin I-Converting Enzyme Gene Is Associated With Coronary Artery Plaque Calcification As Assessed by Intravascular Ultrasound

Pfohl, Martin; Athanasiadis, Anastasios; Koch, Matthias; Clemens, Pia; Benda, Norbert; Häring, Hans Ulrich; Karsch, Karl R.

doi:10.1016/s0735-1097(98)00044-8

Cited by 48 publications

(29 citation statements)

References 30 publications

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“…Pfolhl et al (25) observed a higher incidence and greater extent of coronary lesion calcification, as determined by intravascular ultrasound, in 46 of 146 patients with the DD genotype of the ACE gene. Kardia et al (26) did not find that the apolipoprotein E (apoE) genotypes predicted the presence of CAC in a sample of 329 men and women.…”

Section: Discussionmentioning

confidence: 97%

Familial Aggregation of Coronary Artery Calcium in Families With Type 2 Diabetes

Bowden²,

et al. 2001

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Type 2 diabetes is widely recognized as a major risk factor for atherosclerotic cardiovascular disease, including subclinical atherosclerosis as measured by noninvasive procedures. However, the role of genetic factors that contribute to various measures of subclinical atherosclerosis is largely unknown. We hypothesize that subclinical atherosclerosis, measured as coronary artery calcification (CAC), will be extensive in individuals with type 2 diabetes and that its presence depends on both genetic and environmental factors. The genetic factors should result in the familial aggregation of CAC. To determine the extent of familial aggregation of CAC in the presence of type 2 diabetes, we studied 122 individuals with type 2 diabetes (mean age 60 years) and 13 individuals without diabetes in 56 families. CAC was measured by fast-gated helical computed tomography. Other measured factors included blood pressure, body size, lipids, HbA 1c , and self-reported medical history. To test for an association between CAC and these factors while accounting for the potential familial correlation of CAC, generalized estimating equations were used. CAC was detectable in 80% of individuals with diabetes (median score 84, range 0 -5,776). Extent of CAC, adjusted for age, was positively associated with male sex (P ‫؍‬ 0.0003), reduced HDL (P ‫؍‬ 0.02), albumin-to-creatinine ratio (P ‫؍‬ 0.008), and cigarette pack-years (P ‫؍‬ 0.03). CAC was also positively associated with a history of angina, myocardial infarction, stroke, and vascular procedures (all P < 0.01). HbA 1c and fasting glucose were positively, but nonsignificantly, associated with the extent of CAC (P ‫؍‬ 0.14 and 0.08, respectively). CAC, adjusted for age, sex, race, and diabetes status, was heritable (h 2 ‫؍‬ 0.50; P ‫؍‬ 0.009). In multivariate analysis with additional adjustment for HDL, BMI, hypertension, and smoking, h 2 ‫؍‬ 0.40 (P ‫؍‬ 0.038). These results suggest that strong (independent) genetic factors as well as environmental factors contribute to the variance of CAC in individuals with type 2 diabetes. In these data, CAC seems heritable and may serve as an important feature in designing studies to map genes contributing to both atherosclerosis and type 2 diabetes. Diabetes 50:861-866, 2001

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Section: Discussionmentioning

confidence: 97%

Familial Aggregation of Coronary Artery Calcium in Families With Type 2 Diabetes

Bowden²,

et al. 2001

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“…Pfohl et al 27 reported an association between the insertion/deletion polymorphism of the angiotensin I-converting enzyme gene and CAC detected by intravascular ultrasound in patients with angiographically documented CAD. Apolipoprotein E genotype was found to influence the relationship between risk factors and EBCT-measured CAC presence in ECAC Study participants.…”

Section: Discussionmentioning

confidence: 99%

Heritability of Coronary Artery Calcium Quantity Measured by Electron Beam Computed Tomography in Asymptomatic Adults

et al. 2002

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Background-Electron beam computed tomography is an accurate, noninvasive method to detect and quantify coronary artery calcification (CAC), a marker of subclinical and clinical coronary artery atherosclerosis. CAC quantity predicts future coronary artery disease end points in asymptomatic adults, but measured risk factors explain less than half the variability in CAC quantity. Although several candidate genes for CAC have been identified, the relative importance of genetic influences on CAC quantity has not been assessed in asymptomatic adults in a community. Methods and Results-We quantified the relative contributions of measured risk factors and genetic influences on CAC quantity measured by electron beam computed tomography in 698 asymptomatic white adults from 302 families. Before adjusting for any risk factors, 43.5% of the variation in CAC quantity was attributable to genetic factors (Pϭ0.0007). Independent predictors of CAC quantity were identified with stepwise linear regression. After adjusting for these risk factors, including age, sex, fasting glucose level, systolic blood pressure, pack-years of smoking, and LDL cholesterol, 41.8% of the residual variation in CAC quantity was attributable to genetic factors (Pϭ0.0003). Conclusions-These results demonstrate the importance of genetic factors in subclinical coronary atherosclerosis variation as measured by CAC quantity. The presence of genetic effects suggests that unknown genes that influence CAC quantity are yet to be identified. (Circulation. 2002;106:304-308.)

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“…63 This finding suggested the existence of a possible interaction between cardiovascular risk factors and the ACE polymorphism with respect to carotid IMT. The association between ACE genotype and atherosclerosis was also assessed using coronary calcification as a measure of coronary atherosclerosis, 64,65 and autopsy measurements of aortic atherosclerosis, 66,67 but the results were discordant. In general, a modest positive association between the D allele and atherosclerosis is expected, particularly in those who carry other (genetic or environmental) cardiovascular risk factors.…”

Section: Ace I/d Polymorphism and Atherosclerosismentioning

confidence: 99%

ACE Polymorphisms

Sayed‐Tabatabaei

Oostra

Isaacs

et al. 2006

Circulation Research

381

334

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Abstract-Angiotensin converting enzyme (ACE) plays an essential role in two physiological systems, one leading to the production of angiotensin II and the other to the degradation of bradykinin. The wide distribution and multifunctional properties of these peptides suggest that ACE could be involved in various pathophysiological conditions. The discovery that ACE levels are under genetic control ushered in a new era of investigation; most studies focused on an insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene as a marker for a functional polymorphism. Recently, many single nucleotide polymorphisms were detected in the gene and the search for the locations of functional polymorphisms became a topic of extensive investigation. Nevertheless, association studies on the I/D polymorphism and clinical outcomes continued, mostly with conflicting results. This article reviews the current state of knowledge regarding ACE polymorphisms and suggests that a functional polymorphism is most likely located between intron 18 and the 3Ј UTR. The potential existence of another functional polymorphism in the 5Ј UTR, however, cannot be excluded. This review also presents an overview of ACE function in different pathophysiological systems, and summarizes previous reports on ACE and clinical outcomes. Although findings on the I/D polymorphism and disorders like diabetic nephropathy and Alzheimer disease can be considered conclusive, reports on most of the cardiovascular phenotypes are still controversial. Genotypic and phenotypic misclassifications, insufficient power in some studies, and the presence of interaction with other genes or environmental factors are possible explanations for the contradictory findings.

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Insertion/Deletion Polymorphism of the Angiotensin I-Converting Enzyme Gene Is Associated With Coronary Artery Plaque Calcification As Assessed by Intravascular Ultrasound

Cited by 48 publications

References 30 publications

Familial Aggregation of Coronary Artery Calcium in Families With Type 2 Diabetes

Familial Aggregation of Coronary Artery Calcium in Families With Type 2 Diabetes

Heritability of Coronary Artery Calcium Quantity Measured by Electron Beam Computed Tomography in Asymptomatic Adults

ACE Polymorphisms

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