Angiotensin I-converting Enzyme Genotype Research Articles

Insertion/Deletion Polymorphism of Angiotensin I-converting Enzyme Gene Is Linked With Chromophobe Renal Cell Carcinoma

To study the putative significance of angiotensin I-converting enzyme (ACE) in renal cell carcinoma (RCC). Recent evidence has suggested that a 287-base pair insertion (I)/deletion (D) polymorphism (rs4646994) of the angiotensin I-converting enzyme (ACE) might be associated with cancer risk and progression. The present case-control study accrued 383 subjects, including 210 with RCC and 173 age- and sex-matched healthy individuals without evidence or a history of cancer. Genomic DNA was extracted from the peripheral blood leukocytes. The ACE fragment containing the polymorphism was amplified using conventional polymerase chain reaction using specific primer pairs and subsequently genotyped using agarose gel electrophoresis. Overall, a DD genotype and D allele were more frequently noted in the patients with RCC than in the controls (P = .042 and P = .045, respectively), and resulted from a greater frequency of DD and D in chromophobe RCC (P = .023 and P = .020, respectively). In contrast, the genotype and allele distribution of the controls and patients with papillary or clear cell RCC was similar. The II genotype was not observed in any patient with chromophobe RCC. On multivariate logistic regression analysis, the ACE genotype was an independent risk factor for chromophobe RCC (P = .012). Neither the ACE genotypes or alleles were associated with the tumor stage or grade. The results of the present study have shown for the first time that the ACE insertion/deletion gene polymorphism rs4646994 might be linked with the development of chromophobe RCC. Neither the ACE genotypes nor the alleles were associated with RCC progression.

Effect of ACE genotype on blood pressure and sodium response in a multi‐ethnic population

The insertion allele of the Angiotensin-I Converting Enzyme (ACE) Insertion/Deletion (I/D) polymorphism has been associated with salt-sensitive hypertension. The objective was to determine the effe...

Is there a gender difference between ACE gene and race distance?

We aimed to examine the association between the angiotensin I-converting enzyme (ACE) gene (insertion (I) and deletion (D)) polymorphism in Japanese university track athletes and race distance, as well as to evaluate the gender effects on this association. The ACE I/D allele frequency was determined in 277 athletes (176 men, 101 women; aged 19.7 +/- 1.2 years), who were then grouped on the basis of their major competitive race distances (short distance (SD), < or = 200 m; middle distance (MD), 400-800 m, and long distance (LD), > or =1500 m). The ACE I allele frequency increased with the distance (44.4%, 48.4%, and 66.2% for the SD (n = 107), MD (n = 62), and LD (n = 108) groups, respectively; p < 0.001, chi(2) test). On multinomial logistic regression analysis, significant associations between ACE genotype and race distance were observed only in male athletes (ID vs. SD, p = 0.004; ID vs. LD, p = 0.030; II vs. LD, p = 0.001). There was no significant association between ACE genotype and race distance in female athletes. We conclude that the ACE I allele is overrepresented in endurance athletes, and that its frequency varies depending on gender.

Angiotensin-I Converting Enzyme Genotype Does Not Strongly Correlate With Elite Endurance Athlete Status In Ethiopians

There has been considerable interest over recent years in the use of the Angiotensin-I Converting Enzyme (ACE) gene as a marker of athletic performance. A previous study found no difference in ACE polymorphism between elite Kenyan endurance runners and demographically-matched controls (Scott et al. Comp Biochem Physiol A Mol Integr Physiol 141(2):169-175, 2005), a result that was somewhat surprising in view of contrasting findings in Caucasian populations. PURPOSE: To investigate the association between ACE polymorphisms and elite endurance athlete status in Ethiopians. METHODS: DNA was extracted from buccal swabs collected from 114 members of the Ethiopian national athletics team (E), 315 individuals representative of the general Ethiopian population (C), and 93 individuals from the Arsi region (A), where the majority of elite Ethiopian distance runners originate. RESULTS: There were no significant deviations from Hardy-Weinberg equilibrium in athletes or controls. Ethiopian athletes did not differ significantly from general controls (P = 0.076) or Arsi (P = 0.87) in their ACE ID genotype frequencies (E: 16% II, C: 8% II, A: 13% II). The tendency towards significance in ID genotype frequency between athletes and general controls was not replicated in ACE 22982 genotype (E: 13% AA, C: 12% AA, A: 13% AA), where no significant differences were found (E vs C: P = 0.95, E vs A: P = 0.73). CONCLUSIONS: As previously shown in elite Kenyan athletes, the ACE genotype is not directly associated with elite endurance status in Ethiopians. The tendency towards significance in ID genotype frequency between athletes and general controls may be a reflection of the region of Arsi where the majority of Ethiopian athletes originate. Research part-funded by The Royal Society, The Carnegie Trust for the Universities of Scotland, and The Wellcome Trust

Renin‐angiotensin system inhibitors, angiotensin I‐converting enzyme gene insertion/deletion polymorphism, and cancer

Angiotensin I-converting enzyme (ACE) inhibitors, angiotensin II antagonists, and the ACE insertion/deletion (I/D) gene polymorphism all influence serum angiotensin II action. Because angiotensin II levels have been associated with cancer, the objective of the current epidemiologic study was to investigate whether renin-angiotensin system inhibitors and/or ACE genotypes were associated with an altered risk of colorectal, lung, breast, and prostate cancer. Data were obtained from the Rotterdam Study, a population-based, prospective cohort study with 7983 participants. Participants who had a history of 1 of the cancers of interest (n = 216) or who had a medication history <6 months (n = 88) were excluded, leaving 7679 participants, of whom the ACE genotypes could be assessed in 6670 individuals. The mean follow-up was 9.6 years, during which 730 incident cancers occurred. The effect of medication, ACE I/D genotypes, and their interaction on cancer risk and progression was studied by using Cox proportional hazard models. Carriers of the high-activity genotype DD had an increased risk of breast cancer compared with low-activity II/ID genotype carriers (hazard ratio [HR], 1.47; 95% confidence interval [95% CI], 1.05-2.04), but no association was demonstrated for other cancers. DD carriers who were exposed to long-term and high-dose medication were at lower risk for cancer (HR, 0.28; 95% CI, 0.10-0.79). Short-term, high-dose users were at risk for colorectal cancer progression in the II/ID stratum (HR, 3.83; 95% CI, 1.67-8.79). Renin-angiotensin system-inhibiting drugs seemed to protect against cancer in individuals with the DD genotype, which was associated with high levels of ACE.

Modification of the Coronary Artery Disease Risk Associated with the Presence of Traditional Risk Factors by Insertion/Deletion Polymorphism of theACEGene

Cigarette smoking, hypercholesterolemia, and obesity influence the renin-angiotensin system (RAS) functions including an increased synthesis of the angiotensin I converting enzyme (ACE). Thus in the present work we explore the interactions of the ACE gene insertion/deletion (I/D) polymorphism and traditional risk factors. The study cohort included 341 subjects composed of 172 patients with angiographically confirmed CAD and 169 blood donors without a history of cardiovascular diseases. The I/D polymorphism was genotyped using polymerase chain reaction (PCR) methodology. To determine the interactions between the ACE genotypes and traditional risk factors the epidemiologic approach was used (4 x 2 tables and the synergy measures). The frequency of the DD genotype was significantly higher in patients than in controls (33.7% versus 21.3%, odds ratio [OR] = 1.88, 95% CI; 1.13-3.15, p = 0.010), but greater differences were found in males (35.7% versus 20.5%, OR = 2.15, 95% CI: 1.14-4.04, p = 0.010). We found a synergy of the DD genotype with smoking (SI = 1.88, SIM = 1.22), total cholesterol > or =5 mmol/l (SI = 2.12, SIM = 1.31) and elevated low density lipoprotein (LDL) cholesterol level (> or =3 mmol/l) (SI = 1.78, SIM = 1.14). The presence of the D allele (DD + ID subjects) also increased the risk of coronary artery disease (CAD) associated with the presence of elevated total cholesterol and LDL cholesterol (SI = 1.69, SIM = 1.18, in both cases), elevated level (> or =1.7 mmol/l) of triacylglycerols (SI = 1.81, SIM = 1.18) and overweight/obesity (SI = 4.25, SIM = 2.36). In each case the estimated CAD risk was greater than that predicted by assuming the additivity of effects (the risk increased from 69% for the D allele - total cholesterol interaction to 325% for the D allele - overweight/obesity). The statistical significance was also confirmed by a multiplicative model of synergy. The DD genotype/D allele of the ACE gene increases the risk of CAD associated with the presence of traditional risk factors.

ACE ID genotype affects blood creatine kinase response to eccentric exercise

Unaccustomed exercise may cause muscle breakdown with marked increase in serum creatine kinase (CK) activity. The skeletal muscle renin-angiotensin system (RAS) plays an important role in exercise metabolism and tissue injury. A functional insertion (I)/deletion (D) polymorphism in the angiotensin I-converting enzyme (ACE) gene (rs4646994) has been associated with ACE activity. We hypothesized that ACE ID genotype may contribute to the wide variability in individuals' CK response to a given exercise. Young individuals performed maximal eccentric contractions of the elbow flexor muscles. Pre- and postexercise CK activity was determined. ACE genotype was significantly associated with postexercise CK increase and peak CK activity. Individuals harboring one or more of the I allele had a greater increase and higher peak CK values than individuals with the DD genotype. This response was dose-dependent (mean +/- SE U/L: II, 8,882 +/- 2,362; ID, 4,454 +/- 1,105; DD, 2,937 +/- 753, ANOVA, P = 0.02; P = 0.009 for linear trend). Multivariate stepwise regression analysis, which included age, sex, body mass index, and genotype subtypes, revealed that ACE genotype was the most powerful independent determinant of peak CK activity (adjusted odds ratio 1.3, 95% confidence interval 1.03-1.64, P = 0.02). In conclusion, we indicate a positive association of the ACE ID genotype with CK response to strenuous exercise. We suggest that the II genotype imposes increased risk for developing muscle damage, whereas the DD genotype may have protective effects. These findings support the role of local RAS in the regulation of exertional muscle injury.

The ACE deletion allele is associated with Israeli elite endurance athletes

An Alu insertion (I)/deletion (D) polymorphism in the angiotensin I converting enzyme (ACE) gene has been associated with ACE activity. Opposing effects on elite athletic performance have been proposed for the I and D alleles; while the D allele favours improved endurance ability, the I allele promotes more power‐orientated events. We tested this hypothesis by determining the frequency of ACE ID alleles amongst 121 Israeli top‐level athletes classified by their sporting discipline (marathon runners or sprinters). Genotyping for ACE ID was performed using polymerase chain reaction on DNA from leucocytes. The ACE genotype and allele frequencies were compared with those of 247 healthy individuals. Allele and genotype frequencies differed significantly between the groups. The frequency of the D allele was 0.77 in the marathon runners, 0.66 in the control subjects (P= 0.01) and 0.57 in the sprinters (P= 0.002). The ACE DD genotype was more prevalent among the endurance athletes (0.62) than among the control subjects (0.43, P= 0.004) and the power athletes (0.34, P= 0.004). In the group of elite athletes, the odds ratio of ACE DD genotype being an endurance athlete was 3.26 (95% confidence interval 1.49–7.11), and of ACE II genotype was 0.41 (95% confidence interval 0.14–1.19). We conclude that in Israeli elite marathon runners the frequency of the ACE D allele and ACE DD genotype seems to be higher than in sprinters, suggesting a positive association between the D allele and the likelihood of being an elite endurance athlete in some ethnic groups.

Haplotype of growth hormone and angiotensin I-converting enzyme genes, serum angiotensin I-converting enzyme and ventricular growth: pathway inference in pharmacogenetics

An insertion/deletion (I/D) polymorphism in the angiotensin I-converting enzyme (ACE) gene is associated with variations in circulating and tissue angiotensin I-converting enzyme activity, and differences in exercise-induced left ventricular hypertrophic response. A genetic marker (CSH1.01) in the syntenic GH-CSH gene cluster correlates with metabolic syndrome in adult life in males. Approximately 24% linkage disequilibrium between CSH1.01T and D alleles of ACE I/D has also been reported. The objective was to examine the hypothesis that effects ascribed to ACE genotype may reflect causality in the GH-CSH cluster. The ACE I/D polymorphism and GH-CSH BglII-B single nucleotide polymorphism (in strong linkage disequilibrium with CSH1.01) were determined in 847 British Army recruits. Serum angiotensin I-converting enzyme activity and left ventricular mass were measured before and after a 12-week physical training program. Genotype and haplotype analyses of both markers were performed in relation to these phenotypes. The ACE I/D polymorphism was in linkage disequilibrium with BglII-B (D'=0.3). Strong association was seen between ACE I/D genotypes and serum angiotensin I-converting enzyme activity (P<0.0001), but not left ventricular mass change. BglII-B genotypes also associated significantly with serum angiotensin I-converting enzyme level (P<0.0001). Haplotype analysis, however, showed that most of this association resulted from linkage disequilibrium between BglII-B and ACE I/D. BglII-B did not associate with left ventricular mass change. GH-CSH BglII-B genotype associates significantly with angiotensin I-converting enzyme levels, but only through linkage disequilibrium with ACE I/D. Every phenotype with which ACE I/D has been associated merits investigation of potential causal effects originating in the GH-CSH cluster (and vice versa), otherwise the chain of causality could be misinterpreted.

Angiotensin I-Converting Enzyme: A Pathogenetic Role in Diabetic Renal Damage?

The renin-angiotensin aldosterone system (RAAS) is well-established to be involved in diabetic nephropathy. Several abnormalities in the RAAS have been described in diabetes mellitus, including an abnormal aldosterone to renin ratio, elevated angiotensin I-converting enzyme (ACE) levels, and altered angiotensin II sensitivity. Whereas the renoprotective properties of ACE-inhibition in diabetic nephropathy have been demonstrated more than a decade ago, somewhat surprisingly, the role of ACE-activity in the pathogenesis of diabetic nephropathy is not well established. This paper addresses the possible functional impact of genetic and environmental increased in ACE activity in the pathogenesis of diabetic renal damage, in the context of the various other abnormalities in the RAAS in diabetes. Human and experimental data on circulating and tissue ACE in diabetes are reviewed, as well as the associations of ACE with angiotensin I conversion, with pathophysiological responses, and with renal end organ damage. New data from our laboratory provide evidence for interaction between genetical regulation of ACE activity by the ACE (I/D) genotype and diabetes as an environmental factor. Moreover, for functional effects of the elevated ACE activity in terms of increased conversion of angiotensin I to angiotensin II. The effects of enhanced generation of angiotensin II are modulated by the angiotensin II-subtype I receptor (AT1R). Altered AT1R sensitivity has been reported in diabetes that may further modu-late the eventual effects of elevated ACE. Epidemiological data on the association of genetically elevated ACE activity with diabetic nephropathy provide support for a pathogenetic role of elevated ACE activity in diabetic nephropathy. Together, the data suggest that differences in ACE expression and activity, resulting from both genetic and environmental factors and their interaction can modulate the pathogenesis of diabetic nephropathy. Unravelling the nature of this interaction, with focus on modifiable environmental factors, may help to ameliorate the risk for nephropathy in diabetes.

Angiotensin converting enzyme gene polymorphisms do not predict the course of idiopathic nephrotic syndrome in Swiss children

Contradictory reports exist about a correlation of angiotensin I converting enzyme (ACE) gene polymorphisms to the outcome of idiopathic nephrotic syndrome (INS) in children. We investigated the frequency of ACE polymorphisms and their impact on the clinical course of INS in children in a Swiss hospital. The ACE gene polymorphism (I, insertion; D, deletion) was assessed in 32 children - 22 with steroid-sensitive INS and 10 with steroid-resistant INS - with a median age at onset of INS of 2.9 years (range 1.1-15.0). Polymerase chain reaction amplification was performed on genomic DNA isolated from blood leucocytes. Results were correlated to clinical course and renal morphology. The ACE genotype was I/I, I/D and D/D in two, 12 and eight patients, respectively, with steroid-sensitive INS, and in one, eight and one patient, respectively, with steroid resistance. Renal morphology, available in 25 patients showed minimal change glomerulopathy in 17 patients (14 steroid-sensitive; three steroid-resistant) and focal segmental glomerulosclerosis in eight (one steroid-sensitive; seven steroid-resistant). There was no significant correlation between ACE genotype and steroid responsiveness, histology or outcome. ACE genotype was I/I, I/D and D/D in none, 12 and five patients, respectively, with minimal change glomerulopathy, and in one, five and two patients, respectively, with focal segmental glomerulosclerosis. Six patients with steroid-resistant nephrotic syndrome went into end stage renal disease; ACE genotype was I/I in one and I/D in five, but none were D/D. In contrast to previous reports, ACE gene polymorphism is irrelevant for clinical outcome, steroid responsiveness or morphology in Swiss children with INS.

The Impact of ACE Genotype on Serum ACE Activity in a Black South African Male Population

The strong association between the angiotensin I-converting enzyme (ACE) gene I/D polymorphism with serum ACE activity appears lacking in Nigerians and Kenyans, but has not previously been well assessed in others of African origin. This study addressed this issue in an ethnically well defined black South African population. A putative association for the A22982G ACE gene variant, a QTL likely to impact on serum ACE activity, was also sought. Subjects were 200 healthy male black South African volunteers from the Xhosa ethnic group. Venous blood was obtained from all subjects for DNA extraction. ACE I/D and A22982G genotypes were determined and serum ACE activity measured. Age and blood pressure were recorded. For the group as a whole (mean +/- SD age 38.5 +/- 9.8 years, SBP 119.6 +/- 14.1 mmHg, DBP 78.2 +/- 10.1 mmHg) serum ACE activity was 38.2 +/- 11.2 nmol ml(-1)min(-1). ACE I/D genotype was not significantly associated with serum ACE activity. In contrast, the A22982G variant was significantly associated with serum ACE activity, being 35.9 +/- 9.6, 38.1 +/- 10.6 and 42.4 +/- 15.3 nmol ml(-1)min(-1) for AA, AG and GG genotypes respectively; p = 0.03 by ANOVA and p = 0.01 by linear trend. In keeping with the findings in some other African populations, the ACE I/D polymorphism is not strongly associated with serum ACE activity in Xhosa South Africans. As such, it cannot be used as a marker of ACE activity in these subjects. In this regard the use of the A22982G gene variant may be more appropriate.

Angiotensin I-converting enzyme gene polymorphism modifies the smoking–cancer association: the Hisayama Study

We examined the long-term contribution of smoking and angiotensin I-converting enzyme (ACE) gene I/D polymorphism to total cancer deaths in a prospective study of a general Japanese population. A total of 937 subjects aged 40 years or older were selected from an original cohort of 1621 subjects and were followed up for 32 years. During the follow-up period, 176 subjects died of cancer. Cancer mortality increased significantly with increasing current smoking levels. Although no clear relationship was observed between ACE genotypes and fatal cancer, the interaction term between current smoking and ACE genotype DD was found to be significant. In stratified analysis by ACE genotype after controlling for age, sex, alcohol intake, body mass index, glucose intolerance, serum total cholesterol and systolic blood pressure, the risk of fatal cancer in currently smoking subjects with genotype DD was twofold greater than that in subjects with genotypes II and ID. Among current smokers, subjects with genotype DD also showed a significantly greater risk of death due to cancer compared with those with genotypes II and ID combined (hazard ratio 1.77; 95% confidence interval 1.04-3.00; P=0.03). In conclusion, our findings suggest that ACE genotype DD enhances the association between smoking and cancer death in the general population.

Renin–angiotensin system gene polymorphisms: association with susceptibility to Henoch–Schonlein purpura and renal involvement

The clinical course of Henoch-Schönlein Purpura (HSP) in children is variable, with some patients having a much more rapidly progressing course than others. We investigated whether polymorphisms of the renin-angiotensin system (RAS) genes are involved in HSP. Three RAS genotypes were examined in 114 children with HSP and in 164 healthy children: the angiotensin I converting enzyme (ACE) insertion/deletion polymorphism, the M235T mutation in the angiotensinogen gene (Agt), and the A1166C in the angiotensin II type I receptor (AT1R) gene. Significant differences were observed between HSP patients and control group in the frequency of ACE and Agt genotypes (p=0.004 and p=0.003, respectively). The TT genotype of Agt gene was associated with a 3.5-fold increased risk for Henoch-Schönlein nephritis (HSN) compared with the MM/MT genotype (odds ratio, 3.5; 95% confidence interval, 1.2-10.4). There was a trend to a higher prevalence of the TT genotype of the Agt gene among patients with nephrotic range proteinuria when compared to the patients with mild proteinuria, although the difference did not reach a statistical significance. The results of this study suggest that polymorphisms of ACE gene and Agt gene likely influence the risk of developing HSP. However, among the three genes of the RAS studies, only Agt gene was associated with the susceptibility to HSN. RAS gene polymorphisms studied are not associated with the presence of nephrotic range proteinuria. Additional studies are warranted to verify the correlation between RAS gene polymorphisms and susceptibility to HSP.

The Angiotensin I–Converting Enzyme Gene Insertion/Deletion Polymorphism Is Linked to Early Gastric Cancer

The insertion/deletion polymorphism of the angiotensin I-converting enzyme (ACE) gene has recently been linked to the pathogenesis and progression of human cancers. Using genomic DNA from 88 patients with early gastric cancer confined either to mucosa (pT(1a)) or submucosa (pT(1b)), we assessed the insertion (I) and deletion (D) polymorphism by PCR analysis and compared it with a large noncancer control population (n = 145). In the noncancer control group, the II genotype was observed in 33 (23%) individuals, whereas the ID and DD genotypes were found in 72 (50%) and 40 (27%) individuals, respectively. Interestingly, in the cancer group, we found the II genotype in six (7%) patients and the ID genotype in 46 (52%) individuals, whereas the DD genotype was observed in 36 (41%) individuals (P = 0.0034). Accordingly, the odds ratio for the II genotype was 0.20 [95% confidence interval (95% CI), 0.08-0.54; P = 0.009] and 0.55 for the ID/II genotype (95% CI, 0.31-0.96; P = 0.044) using the high-activity genotype DD as the reference category. No correlation was found among tumor type, tumor stage, the presence of Helicobacter pylori, and the ACE genotype. Our study provides further evidence that the ACE insertion/deletion gene polymorphism may be linked to the development of early gastric cancer.

Reduction of Pneumonia Risk by an Angiotensin I–Converting Enzyme Inhibitor in Elderly Japanese Inpatients According to Insertion/Deletion Polymorphism of the Angiotensin I–Converting Enzyme Gene

We have reported that use of angiotensin I-converting enzyme (ACE) inhibitor, which is a class of antihypertensive agent that induces cough, is an independent factor in reducing risk of pneumonia among elderly inpatients. Insertion/deletion (I/D) polymorphism of the ACE gene (ACE) has been associated with the risk of pneumonia in elderly individuals. However, the ability of ACE inhibitors to reduce pneumonia-related morbidity in individuals with the ACE polymorphism is unclear. Therefore we determined the association of ACE inhibitor use and ACE genotypes with reduction of pneumonia risk in the Japanese elderly population. We conducted a hospital-based, retrospective, case-control study to evaluate the effect of an ACE inhibitor and ACE polymorphism on incidence of pneumonia. Case subjects were pneumonia patients (N = 105) >or=65 years of age, during an 8-month period of a nonwinter season. Control subjects (n = 420) were elderly patients who were frequency matched to the case subjects by age (within +/- 2 years) and gender. Data were collected on medication with the ACE inhibitor temocapril and on known risk factors for pneumonia. The significances of differences for the risk factors were analyzed using univariate and multivariate comparisons of the case and control subjects. After adjustment for potential confounders by multiple logistic regression analysis, the odds ratio (OR) estimates for pneumonia were 0.458 (95% confidential interval [CI]: 0.230 to 0.909, P = .026) for ACE inhibitor use. Conditional logistic regression analysis according to ACE genotypes revealed significant reduction of pneumonia risk by use of temocapril compared with that in nonhypertensive individuals (ie, the reference group) in those with ACE ID + II (OR: 0. 416, 95% CI: 0.177 to 0.976, P = .044), but not in those with ACE DD (OR: 0.706, 95% CI: 0.198 to 2.518, P = .592). These results suggest that use of an ACE inhibitor is beneficial for reducing risk of pneumonia, particularly in individuals with the ACE genotypes ID + II.

Angiotensin Converting Enzyme Gene Polymorphism in Egyptian Patients with Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) shows various clinical manifestations with various immunological abnormalities. The development of lupus nephritis and vasculitis is common in patients with SLE. As angiotensin I-converting enzyme (ACE) has been reported to be associated with various immunological phenomena, we investigated the correlation between insertion(I) / deletion(D) polymorphism of the ACE gene and SLE. Fifty Egyptian patients with SLE and thirty healthy control persons were involved in this study. ACE gene was detected by the polymerase chain reaction (PCR). In SLE patients, there is a significant difference when comparing DD and II genotypes (P<0.05),being higher in the DD genotype. And a highly significant difference when comparing ID and II genotypes (P=0.001), being much higher in ID genotype than II genotype. According to vasculitis, there is a significant relationship between vasculitis and patients genotypes when comparing ID genotype with both II and DD genotypes (P<0.05), being highest in ID genotype. There is a significant relationship found when comparing ID genotype with both II and DD genotypes, being highest in ID genotype in patients with score ≥21. These results suggest that the ACE genotype could be associated with SLE.

The Number of Lymph Node Metastases in Gastric Cancer Correlates with the Angiotensin I–Converting Enzyme Gene Insertion/Deletion Polymorphism

In the present study, we aimed to substantiate the putative significance of angiotensin I-converting enzyme (ACE) on gastric cancer biology by investigating the influence of its gene polymorphism on gastric cancer progression. Genomic DNA was purified from peripheral blood mononuclear cells or tissue specimens. Amplified ACE gene fragments were separated on agarose gels. D or I alleles were identified by the presence of 190- or 490-bp fragments, respectively. Local expression of ACE was investigated by immunohistochemistry. Twenty-four of 113 (21%) gastric cancer patients had the II, 57 (51%) the ID, and 32 (28%) the DD genotype. The distribution of the ACE genotypes did not differ significantly from the control group of 189 patients without gastric cancer. However, the ACE genotypes correlated with the number of lymph node metastases and the Unio Internationale Contra Cancrum (UICC) tumor stage. Patients with the II genotype had a highly significantly smaller number of lymph node metastases (P < 0.001) and a significantly lower UICC tumor stage (P = 0.01) than patients with the DD genotype. No correlation was found between tumor type, tumor location, local tumor growth, distant metastases, and the ACE genotype. The expression of ACE in gastric cancer was investigated by immunohistochemistry in 100 of 113 patients. ACE was expressed by endothelial cells in all (100%) specimens and by tumor cells in 56 (56%) specimens. Our study shows that ACE is expressed locally in gastric cancer and that the gene polymorphism influences metastatic behavior.

The Influence of Angiotensin-Converting Enzyme Gene of Donor and Recipient on the Function of Transplanted Kidney

One of the genes that is supposed to influence renal graft function is the one encoding angiotensin I-converting enzyme (ACE). It shows polymorphism in the presence (I allele) or absence (D allele) of a 287-base pair fragment. The question arises whether ACE gene polymorphism of the recipient and donor influences renal graft survival. This prospective study included 94 recipients who underwent ACE genotyping (DD, DI, II) and measured their creatinine clearance after cimetidine administration. These factors were correlated with the occurrence of acute or chronic rejection and of pharmacologic treatment of hypertension. In 27 recipients it was possible to obtain the ACE genotype of the donor. Among the recipients, 36 proved to be DD genotype, 38 ID, and 20 II. Among the donors, 10 proved to be DD genotype, 10 ID, and 7 II. The changes in creatinine clearance after cimetidine administration were not significantly different among any of the genotype subgroups. Significantly higher creatinine concentrations were found among recipients with II genotype compared to the combined group of ID and DD among patients not treated with ACE inhibitors, but not among those receiving ACE I after kidney transplantation. No differences were found in the frequency of rejection episodes among the subgroups with different ACE genotypes. No significant influence of donor ACE genotype on renal graft function was observed. In summary, the I/D genotype was not an independent prognostic factor for renal graft survival in the first 4 years after transplantation. Possibly the use of ACE I alters the influence of genotype on some parameters.

Performance at altitude and angiotensin I-converting enzyme genotype

The "insertion" (I) rather than "deletion" (D) variant of the human angiotensin-converting enzyme (ACE) gene is associated with both lower tissue ACE activity and elite performance at high altitude. We examined whether the onset of acute mountain sickness (AMS), and further performance on reaching the summit of Mt. Blanc are influenced by the ACE I/D polymorphism. Two hundred and eighty-four climbers (235 males, [37.0 (11.0 years], (86 DD, 142 ID, 56 II)) had assessment of their AMS status upon arrival to the Gouter hut (3,807 m) on day 1, and again on day 2 after an attempted ascent to the summit of Mt. Blanc (4,807 m). Success in reaching the summit was genotype dependent (87.7% of DD, 94.9% of ID and 100% of II individuals; P=0.048); I allele frequency for those reaching the summit was 0.47 compared to 0.21 for those who did not (P=0.01). The onset of AMS on day 1 appeared to be dependent on genotype (P=0.003), but with those heterozygous being less affected. ACE genotype was not associated either with AMS onset or severity on day 2. Thus, ACE I/D genotype is associated with successful high altitude ascent in this prospective study-an association not explicable by genotype-dependence of AMS onset or severity. Values are given as mean (SD) unless otherwise stated.