BACKGROUND: Researchers have suggested that the deletional allele of the ACE (angiotensin-converting enzyme) gene insertion-deletion polymorphism is a potent risk factor for myocardial infarction. This association could not be confirmed in the Copenhagen City Heart Study, in which 10,150 persons were studied. The ACE gene polymorphism has also recently been suggested as a potent risk factor for ischemic cerebrovascular disease. OBJECTIVE: To investigate the association between ACE gene polymorphism and ischemic cerebrovascular disease. DESIGN: Two case-referent studies and a cross-sectional study. SETTING: University hospital in Copenhagen, Denmark. PARTICIPANTS: Case-referent study 1: 35 women and 38 men who developed ischemic cerebrovascular disease before 50 years of age compared with 1454 women and 1737 men from a general population sample. Case-referent study 2: 82 women and 137 men with ischemic cerebrovascular disease and carotid stenosis greater than 40% compared with 4273 women and 3091 men from the general population sample. Cross-sectional study of the general population sample: 67 women and 93 men with ischemic cerebrovascular disease compared with 4077 women and 3156 men without such disease. MEASUREMENTS: Genotype; age; body mass index; smoking habits; levels of lipids, lipoproteins, apolipoproteins, and fibrinogen; and diagnosis of hypertension, diabetes mellitus, and ischemic cerebrovascular disease. RESULTS: Odds ratios for ischemic cerebrovascular disease by ACE genotype classes were not significantly different from 1.0 in women or men in any of the three studies, separately or combined. In a logistic regression analysis that controlled for age and conventional cardiovascular risk factors, odds ratios in either sex still did not significantly differ from 1.0 in any study, separately or combined. CONCLUSION: In two case-referent studies, a cross-sectional study, and the three studies combined, no statistically significant difference was found in the development of ischemic cerebrovascular disease between genotype classes of the ACE gene polymorphism in women or men.
BACKGROUND AND AIMS: The level of physical functioning (PF) late in life has, in recent years, been shown to be influenced by genetic factors. One of the most extensively studied genetic variants associated with PF and trainability is insertion/deletion (I/D) polymorphism in the gene encoding Angiotensin Converting Enzyme (ACE). However, ACE studies have mainly been conducted among younger persons in excellent physical shape. In this study, we examine whether the level of PF, trainability, or rate-of-change are associated with the ACE genotype among the elderly. METHODS: We used data from 4 randomized training studies of elderly Danes (N = 203). The measures of PF were self-report, maximal oxygen uptake, muscle strength, walking speed, and body composition. RESULTS: Overall, a favorable change in the measures of PF was observed in training groups compared with control groups. However, within groups, neither pre- or post-training/control period levels of PF nor differences in pre- and post-levels were associated with the ACE genotype. CONCLUSIONS: On the basis of our randomized studies, we could not detect any association between the ACE genotype and the level of PF or change, regardless of whether response to physical training or spontaneous changes was studied.
We investigated the association between angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) gene polymorphisms and exercise training responses of resting and exercise blood pressure (BP). BP at rest and during submaximal (50 watts) and maximal exercise tests was measured before and after 20 wk of endurance training in 476 sedentary normotensive Caucasian subjects from 99 families. AGT M235T and ACE insertion/deletion polymorphisms were typed with PCR-based methods. Men carrying the AGT MM and MT genotypes showed 3. 7 +/- 0.6 and 3.2 +/- 0.5 (SE) mmHg reductions, respectively, in diastolic BP at 50 watts (DBP(50)), whereas, in the TT homozygotes, the decrease was 0.4 +/- 1.0 mmHg (P = 0.016 for trend, adjusted for age, body mass index, and baseline DBP(50)). Men with the ACE DD genotype showed a slightly greater decrease in DBP(50) (4.4 +/- 0.6 mmHg) than the II and ID genotypes (2.8 +/- 0.7 and 2.4 +/- 0.5 mmHg, respectively, P = 0.050). Furthermore, a significant (P = 0.022) interaction effect between the AGT and ACE genes was noted for DBP(50); the AGT TT homozygotes carrying the ACE D allele showed no response to training. Men with the AGT TT genotype had greater (P = 0.007) diastolic BP (DBP) response to acute maximal exercise at baseline. However, the difference disappeared after the training period. No associations were found in women. These data suggest that, in men, the genetic variation in the AGT locus modifies the responsiveness of submaximal exercise DBP to endurance training, and interactions between the AGT and ACE loci can alter this response.
Angiotensin-converting enzyme (ACE) genotypes may reflect prognosis in sarcoidosis. They were determined in 59 Finnish sarcoidosis patients and 70 healthy control subjects. The prognosis of the sarcoidosis patients was determined after follow-up for 1, 2, 3, 5 and >5 yrs and classified as good (normal chest radiograph and lung function, no signs of extrapulmonary disease activity within 2 yrs from diagnosis), intermediate (neither good nor poor) or poor (persisting unstable pulmonary infiltrates, vital capacity and diffusing capacity of the lung for carbon monoxide 5 yrs follow-up). The DD, ID and II genotypes were found in 31 and 27%, in 54 and 49%, and in 15 and 24% of patients and control subjects respectively. The odds ratio (DD+ID to II) was 1.45 (95% confidence interval 0.60-3.49). The D alelle was found more often in patients (58%) and in control subjects (51%) than the I allele but the difference was not statistically significant. Statistically significantly more patients with the DD genotype had a poor prognosis compared with patients with II homozygotes and ID heterozygotes. Among 11 patients with Löfgren's syndrome (bilateral hilar lymphadenopathy and erythema nodosum), four had the DD genotype. Three of these patients had a prognosis despite presenting a clinical picture usually associated with a good prognosis. The angiotensin-converting enzyme genotype may be a prognostic marker in sarcoidosis and larger studies are warranted to define its clinical utility.
Earlier epidemiologic studies have yielded inconsistent results on the extent and timing of the blood pressure (BP) increase in offspring of hypertensive parents. We hypothesized that a familial influence on the BP of the offspring exists from birth on, but becomes significant only later in childhood. We studied the influence of familial occurrence of hypertension on the BP of 3596 children aged 6 to 18 years during a 6-year follow-up. In addition, we examined the possible associations of BP variations with polymorphisms of two candidate genes for hypertension, ie, those coding for the angiotensin converting enzyme (ACE) and those coding for angiotensinogen. A positive family history of hypertension was reflected as the occurrence of higher systolic BP values from the age of 9 years and upward among the females and from the age of 12 years and upward among the males. The mean differences in BP varied from 3.2 to 5.8 mm Hg (systolic) and 2.1 to 5.9 mm Hg (diastolic) between the female offspring of normotensive and hypertensive parents and grandparents. The systolic BP values were significantly higher among females with a hypertensive history in two generations in comparison with females from normotensive families. Among the male offspring of hypertensive and normotensive families, the BP differences were inconsistent. The deletion/deletion males had higher systolic BP values than those with other ACE genotypes. In contrast, variation at the angiotensinogen gene locus was not significantly associated with BP. We conclude that parental history of hypertension is a risk factor for high blood pressure among the offspring from the ages of 9 to 12 years and upward, and hypertension within two generations may enhance this effect. Although the common genetic variation of ACE may influence blood pressure in male children and adolescents, our data do not suggest a role for the common variation of the angiotensinogen gene as a BP regulator during childhood.
BACKGROUND: The main objective of this study was to investigate the angiotensin converting enzyme (ACE) genotype as a possible risk factor for migraine (both with and without aura) compared to controls. We also wanted to examine whether a clinical response to an ACE inhibitor, lisinopril, or an angiotensin II receptor blocker, candesartan, in migraine prophylaxis was related to ACE genotype. METHODS: 347 migraine patients aged 18-68 (155 migraine without aura (MoA), 187 migraine with aura (MwA) and 5 missing aura subgroup data) and 403 healthy non-migrainous controls > 40 years of age were included in the study. A polymerase chain reaction (PCR) was performed on the genomic DNA samples to obtain the ACE insertion (I)/deletion(D) polymorphisms. RESULTS: No significant differences between migraine patients and controls were found with regard to ACE genotype and allele distributions. Furthermore, there was no significant difference between the controls and the MwA or MoA subgroups. CONCLUSION: In our sample there is no association between ACE genotype or allele frequency and migraine. In addition, ACE genotype in our experience did not predict the clinical response to lisinopril or candesartan used as migraine prophylactics.
The deletion/deletion genotype of the insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been suggested to be a risk factor for myocardial infarction (MI). The objective of this study was to evaluate whether genotype distributions of the I/D polymorphism of the ACE gene are different between individuals from high-risk and low-risk areas for coronary heart disease in the genetically isolated population of Finland and to assess the impact of this genetic risk factor by comparing individuals with different parental histories of MI. Representative population-based samples of middle-aged men (n = 363) and women (n = 358) from two areas of Finland were used. The area had a borderline significant effect on the prevalence of the genotype DD (beta = 0.35, SE = 0.16, X2 = 470, df = 1, P = 0.03), the DD genotype being more prevalent in eastern Finland (the high-risk area). The II genotype was more prevalent in women with parental history of MI, so we could not replicate the previous findings of the risk-increasing effect of DD genotype in this sample. Although the observed difference in the ACE DD genotype between the high-risk and low-risk areas for coronary heart disease might represent one of the genetic factors contributing to the difference in risk of coronary heart disease between eastern and southwestern Finland, the data emphasize the fact that also other risk factors, including other genes, contribute to this difference and the high incidence of MI in Finland.
The insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene has been postulated to be associated with CAD in some populations of European descent. As part of a study investigating metabolic and genetic factors in subjects with premature coronary artery disease (CAD), we examined the I/D polymorphism of the ACE gene in 134 subjects with premature CAD (105 men and 29 women, mean age 49 +/- 6 years) and 116 control subjects selected for health (71 men, 45 women; mean age 39 +/- 7 years). Both patients and controls were of French Canadian descent. As expected, significant differences were found between cases and controls with respect to age, plasma lipoprotein cholesterol, presence of smoking, diabetes and high blood pressure after correction for age. Multivariate analysis confirms the importance of age, HDL-C levels, smoking and apo B levels as determinants of CAD. Allele frequencies of the I and D polymorphism were 43.1% and 57.9% in controls, and 48.5% and 51.5% in CAD cases (chi 2 = 0.622, p = 0.430). No significant association between the I/D polymorphism and conventional cardiovascular risk factors, including plasma levels of lipids, lipoprotein cholesterol, diabetes or smoking, was found in cases or controls. Furthermore, the presence of the I/D polymorphism did not correlate with a history of hypertension or a family history of premature CAD in CAD patients. We conclude that, in our selected population, the I/D polymorphism of the ACE gene is not associated with CAD, conventional risk factors, or a family history of CAD. Although our sample size does not allow sufficient power to ascertain that the ACE I/D polymorphism is not associated with CAD, we do not recommend the routine measurement of the ACE polymorphism in our population to determine cardiovascular risk.
Reduction in angiotensin-converting enzyme (ACE) activity has been shown to attenuate pancreatic stellate cell activation and pancreatic fibrosis and suggested as a potential treatment for chronic pancreatitis. The ACE gene insertion/deletion (I/D) polymorphism in intron 16 accounts for nearly half the variation in serum ACE levels. This study determined the frequency of the I/D polymorphism in patients with acute and chronic pancreatitis.
In total, 887 patients (346 with alcoholic, 443 with nonalcoholic, and 98 with acute pancreatitis) were enrolled, and were compared with 1294 healthy controls. Genotyping of the I/D polymorphism was performed by PCR or melting curve analyses.
No significant differences were found in the prevalence of the ACE-deletion genotype frequencies when patients with alcoholic (27.5%), nonalcoholic (26.4%), and acute pancreatitis (32.7%) were compared with controls (26.9%). Likewise, allele frequencies of the ACE deletion polymorphism were not significantly different in patients with alcoholic (53.8%), nonalcoholic (50.6%), and acute pancreatitis (54.1%) and controls (52.7%).
The I/D polymorphism of the ACE gene was not found to be associated with acute and chronic pancreatitis.
Association of polymorphic markers G7831A of ACE gene, Lys198Asn of endothelin-1 (EDN1) gene, and 4a/4b of NOS3 gene with characteristics of structure and function of the left ventricle was studied in 70 (31 men and 39 women) natives of Yakutia with hypertension. Mean age of patients was 48.3+/-0.74 years, duration of hypertension -- 12.4+/-0.99 years; 60 (85.7%), 7 (10%) and 3 (4.3%) patients had III, II and I degree of hypertension, respectively. Polymerase chain reaction was used for identification of alleles of polymorphic markers G7831A of ACE gene, Lys198Asn of EDN1 gene, and 4a/4b of NOS3 gene. Polymorphic marker G7831A of ACE gene was not associated with severity of hypertrophy of left ventricular myocardium as well as with state of systolic and diastolic left ventricular function. Patients with allele Asn of EDN1 gene in the genotype had significantly lower value of peak A integral of trans-mitral blood flow. Patients with allele 4a of NOS3 gene had thicker left ventricular walls, greater left ventricular myocardial mass and mass index.