Polymorphism Of Angiotensin I-converting Enzyme Gene Research Articles

Angiotensin-converting enzyme polymorphism and the risk of coronary heart disease in the Saudi male population.

To determine the relevance of angiotensin I-converting enzyme (ACE) gene polymorphism for coronary artery disease (CAD) in the Saudi population. DNA of 84 male Saudi patients with established CAD, 36 male controls who underwent angiography, and 327 healthy Saudi male blood donors was amplified by polymerase chain reaction, using oligonucleotide primers flanking the insertion (I)/deletion (D) sites in the polymorphic region of intron 16 of the ACE gene. Polymerase chain reaction amplification resulted in 490-bp (II), 190-bp (DD), or 490- and 190-bp (ID) fragments. The genotype II distribution was 16.7% in the control group, 7.3% in the blood donor group, and 7.2% in the patients with CAD, and the distribution for DD was 58.3%, 47.1%, and 41.0%, respectively. Notably, 61.9% (P <.0001) of CAD patients presented with angina on admission, and 52.4% had diabetes mellitus. The results show no increased risk of CAD in association with either the II or DD genotypes in the Saudi population. However, further investigation of genotype II as a predictor for atherosclerosis rather than increased risk of coronary heart disease may be indicated.

Elevated Urinary Albumin Excretion is not Linked to the Angiotensin I-converting Enzyme Gene Polymorphism in Clinically Healthy Subjects

An elevated urinary albumin excretion (UAE) in non-diabetic subjects without renal or cardiovascular disease has been shown to be predictive of ischaemic heart disease. An insertion (I)/deletion (D) polymorphism in the angiotensin I-converting enzyme (ACE) gene has been identified and the D allele may be associated with cardiovascular disease. The aim of this study was to find a potential linkage between this polymorphism and elevated UAE. For studies of UAE and cardiovascular pathophysiology, a highly selected population sample has been identified comprising all clinically healthy subjects aged 40-65 years with elevated UAE in a dipstick negative urinary sample (n = 27) from The Copenhagen City Heart Study. Neither the ACE genotype distribution (p = 0.12) nor the D and I allele frequencies (p = 0.69) differed significantly between subjects with elevated UAE and a matched normoalbuminuric control group (n = 46). Elevated UAE in clinically healthy subjects is not linked to the ACE gene polymorphism.

ACE and AT1R gene polymorphisms and hypertension in Indian population

The renin angiotensin system (RAS) controls intrarenal blood pressure and sodium balance, and is an important target for antihypertensive therapy. Several polymorphisms have been identified within genes encoding RAS that may contribute to the development of elevated blood pressure. The relevance of these polymorphisms in hypertension remains controversial. In this study we have examined 105 hypertensive subjects and 192 controls from the Indian population for I/D polymorphism of angiotensin I converting enzyme (ACE) and A(1166)C polymorphism of angiotensin II type I receptor (AT1R) genes by polymerase chain reaction (PCR) and PCR-based restriction enzyme analysis method, respectively. There was no significant difference in the distribution of ACE (I/I, I/D, and D/D) and AT1R (A/A and A/C) genotypes between controls and hypertensive subjects. D allele was significantly associated with an early onset of hypertension and although nonsignificant, the frequency was high in subjects with family history of cardiovascular disorders. C(1166) allele of AT1R did not correlate with the age of onset of hypertension and the frequency was low in subjects with family history. Thus no association was found between ACE and AT1R genotypes and hypertension. However the D allele can be used as a predictor of risk of hypertension in the Indian population.

Angiotensin I-converting enzyme gene polymorphism, coronary artery disease and myocardial infarction. An angiographically controlled study.

We investigated the association between insertion/deletion polymorphism of the angiotensin I-converting enzyme (ACE) gene, the presence and extent of coronary artery disease, and myocardial infarction. The D allele of the ACE gene has been associated with coronary artery disease and myocardial infarction, but this association has been challenged in epidemiological studies. Nine hundred and sixty-nine men and 341 women undergoing coronary angiography were studied. The ACE genotypes were assessed by polymerase chain reaction from genomic deoxyribonucleic acid, homozygosity for the D allele was controlled using an insertion-specific primer. Coronary artery disease was defined by angiographic criteria, the extent of coronary artery disease by the number of coronary arteries with >/=50% lumen narrowing. The ACE genotypes did not differ in terms of age, sex, body mass index, blood pressure, plasma lipids or lipoproteins. We found no association between the ACE genotypes and coronary artery disease (odds ratio, 95% confidence interval in DD genotypes for coronary artery disease in men 0.97, 0.70-1.36; in women 1.56, 0.95-2.57), extent of coronary artery disease (men 1.17, 0.85-1.61; women 1.24, 0.65-2.34), or myocardial infarction among the patients with coronary artery disease (men 1.07, 0.78-1.48; women 0.95, 0.50-1.76). The ACE genotype was not associated with coronary artery disease or myocardial infarction in hypertensives (n=771; odds ratio for coronary artery disease 0.93, 0.65-1.34; odds ratio for myocardial infarction 0.94, 0.66-1.33), or in patients </=60 years (n=649; odds ratio for coronary artery disease 1.05, 0.72-1.52; odds ratio for myocardial infarction 0.96, 0.63-1.47). ACE insertion/deletion gene polymorphism is associated neither with the prevalence nor the extent of coronary artery disease, nor with myocardial infarction in this relatively large sample of Caucasian men and women. Genotyping for ACE insertion/deletion polymorphism is not useful in assessing the individual risk of coronary artery disease or myocardial infarction.

The deletion genotype of the angiotensin I-converting enzyme is associated with an increased vascular reactivity in vivo and in vitro

OBJECTIVESTo define a link between the deletion genotype (DD) and vascular reactivity, we studied in vivo and in vitro phenylephrine (PE)-induced tone and the effect of angiotensin II (AII) at physiological (subthreshold) concentrations on PE-induced tone.BACKGROUNDThe deletion allele (D) of the angiotensin I-converting enzyme (ACE) has been associated with a higher circulating and cellular ACE activity and possibly with some cardiovascular diseases.METHODSDuring cardiac surgery PE-induced contraction was studied in patients with excessive hypotension. In parallel, excess material of internal mammary artery, isolated from patients operated for bypass surgery, was mounted in an organ chamber, in vitro, for isometric vascular wall force measurement.RESULTSIn patients under extracorporeal circulation, PE (25 to 150 μg) induced higher contractions in patients with the DD genotype (e.g., with PE 75 μg: 20.3 ± 2.9 vs. 11.5 ± 2.5 mm Hg/ml per min, DD vs. II/ID, n = 15 vs. 30, p < 0.03). In the mammary artery, in vitro, contractions to PE (0.1 to 100 μmol/liter) or AII (1 or 100 nmol/liter) were not affected by the genotype. Angiotensin II (10 pmol/liter) significantly potentiated PE (1 μmol/liter)-induced contraction in both groups. Potentiation of PE-induced tone by AII was significantly higher in the DD than in the II/ID group.CONCLUSIONSThe DD genotype was associated with an increased reactivity to PE in vivo and potentiating effect of exogenous AII in vitro. The higher response to PE in vivo might reflect a higher potentiation by endogenous AII. These data should be considered to understand possible link(s) between cardiovascular disorders and the ACE gene polymorphism.

Genetic polymorphism of renin-angiotensin system is not associated with diabetic vascular complications in Japanese subjects with long-term insulin dependent diabetes mellitus

In a hospital cohort study, we examined whether or not ACE (Angiotensin-I converting enzyme) and AGT (Angiotensinogen) gene polymorphisms were associated with the development of nephropathy in long-term Japanese insulin-dependent diabetes mellitus (IDDM) patients with or without proliferative retinopathy, and whether or not the polymorphisms were associated with an arteriosclerotic family history in first degree relatives of the patients. A total of 201 patients with IDDM for more than 10 years and 159 patients with IDDM for more than 15 years were randomly selected in our hospital. All patients received uniform diabetes management and were divided into three groups, no nephropathy, incipient nephropathy and clinical nephropathy groups. There were no differences in clinical characteristics excluding urinary albumin to creatinine ratio and systolic blood pressure between the three groups. ACE I/D polymorphism was related to plasma ACE activity, but there were no associations between ACE I/D polymorphism and the development of diabetic nephropathy, nor was renal deterioration observed in patients with proliferative retinopathy even in those with a history of diabetes for more than 15 years. The AGT polymorphism did not have an additive effect on the association between ACE polymorphism and the development of diabetic nephropathy in patients with or without retinopathy. Development of diabetic nephropathy in the patients with or without proliferative retinopathy did not result in ACE or AGT polymorphisms. On the other hand, the ACE DD genotype was associated with a family history of ischemic heart disease in first degree relatives ( χ 2 score=9.04, P<0.05). ACE and AGT gene polymorphisms may not play a role in the protective or accelerative effect against the development of diabetic nephropathy in the patients with or without proliferative retinopathy, but ACE gene polymorphism might be related to an arteriosclerotic family history in Japanese IDDM patients.

Abstracts of literature

Abstracts of literature

Angiotensin I-converting enzyme gene polymorphism in a low-risk European population for coronary artery disease

An insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) has been associated with an increased risk of coronary artery disease (CAD) and myocardial infarction (MI). However, this finding has not been fully investigated in European populations with very low CAD risk. In a case-control study on a population from Southern Europe (Toulouse, France), we evaluated the ACE I/D polymorphism in 405 men, aged 35–65 years, who underwent coronary angiography and in 357 representative control men within the same age range. We also explored associations in the patients between this polymorphism and CAD severity. The ACE genotype was not associated with the presence of either CAD or MI. The ACE genotype was not a marker for angiographically assessed CAD severity. In a sample in one of the European populations with the lowest CAD risk, ACE I/D polymorphism was not associated with an increased risk for CAD or MI and did not influence the extent of CAD.

Angiotensin I-converting enzyme gene polymorphism in myocardial infarction in patients with type 2 diabetes

Insertion/deletion (I/D) polymorphism of angiotensin I-converting enzyme gene (ACE) as a potential marker of genetic susceptibility to myocardial infarction (MI) was studied in 76 patients with non-insulin-dependent diabetes (NIDDM) surviving after MI, 115 NIDDM patients without history of MI, and 165 subjects without diabetes from the general Moscow population. Case-control association study failed to reveal significant differences in distribution of ACE gene alleles and genotypes between patients with and without MI. However, we observed a tendency of I allele frequency to decrease and of D allele frequency to increase in infarction. Moreover, patients with MI had almost the same pattern of I and D allele and DD genotype distribution as normal subjects from general population (34.9, 65.1, and 46.1% vs. 35.8, 64.2, and 48.5%, respectively). On the other hand, diabetics without infarction had a slightly higher prevalence of I allele and I allele-containing genotypes (ID and II) than patients with documented MI (40.4, 46.1, and 17.4% vs. 34.9, 38.2, and 15.7%, respectively) and lower DD genotype frequency (36.5 vs. 46.1%), respectively). Therefore, we suppose that in Moscow a higher incidence of D allele in comparison with I allele and of its genotypes ID and II may be regarded as a genetic protective factor, whereas D allele and DD genotype as a factor of genetic susceptibility to MI in NIDDM patients.

Angiotensin I-converting enzyme gene polymorphism in intracranial saccular aneurysm individuals

A polymorphism in the angiotensin I-converting enzyme (ACE) gene has been associated with cerebrovascular diseases as a new potent risk factor. The purpose of this study was to investigate an association of the gene polymorphism with intracranial saccural aneurysmal patients. The study population consisted of 83 aneurysmal patients (age range 47-85 years) (the AN group) and 704 matched control subjects (age range 30-87 years) (the Control group). For detection of the ACE gene polymorphism, the standard PCR method was performed by using genomic DNA isolated from peripheral blood leukocytes. The PCR products were a 490-bp in the presence of the insertion (I) and a 190-bp fragment in the absence ofthe insertion (0). The ACE gene polymorphism was classified into three genotypes: 1,1 genotype (a 490–bp band); b,o genotype (a 790-bp band); or 1,0 genotype (both a 490–bp and a 190-bp band). The number of subjects with lilt 1/0, and % genotypes was 38, 40, and 5 in, the AN group and 43, 45, and 76 in the Control group, respectively. The frequency of the % genotype in the AN group was significantly lower (5/83 = 0.06) than that in the Control group (76/704 = 0.75) (X2 = 4.06; P = 0.044). There was no significant difference between the genotypes of hypertensive patients and normotensive patients in the AN group. Thus, this present study suggests that genetic heterogeneity of the ACE gene may be correlated with the etiology of intracranial aneurysms. [Neural Res 1998; 20: 607–611]

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

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. 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. 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. 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.

Ambulatory Systolic Blood Pressure is Related to the Deletion Allele of the Angiotensin I Converting Enzyme Gene in Young Normotensives with Parental History of Hypertension

The aim of the present study was to evaluate the relationship between the angiotensin I converting enzyme (ACE) gene polymorphism and ambulatory blood pressure in young normotensive males with (n=45) and without (n=100) family history of hypertension. Twenty-four hour and daytime systolic blood pressure was significantly higher in subjects with a parental history of hypertension. Ambulatory blood pressure values did not differ significantly across ACE genotypes in subjects with negative family history of hypertension. In subjects with a parental history of hypertension, there was a significant positive association between the D allele of the ACE gene polymorphism and 24-h, daytime and nighttime systolic blood pressure. For twenty-four hour systolic blood pressure there was an average 9 mmHg difference between subjects with DD and I1 genotypes. The results indicate that in normotensive subjects with a genetic predisposition to hypertension, ambulatory systolic blood pressure is related to the D allele of the ACE gene.

Angiotensin I-converting enzyme gene polymorphism and acute response to captopril in essential hypertension.

Insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene has been shown to be a determinant for serum ACE level and a marker for several cardiovascular diseases. We investigated whether the ACE gene can predict the therapeutic efficacy of ACE inhibitors in essential hypertensive patients. The response of blood pressure and plasma renin activity (PRA) 1 h after 50 mg captopril administration were evaluated in 82 inpatients with untreated essential hypertension (42 men, 40 women; mean age +/- SD: 52 +/- 13 years; range: 27 to 79 years) in relation to ACE genotypes. There were no differences in age, gender, blood pressure, and PRA in the basal conditions, among essential hypertensive patients with the II, ID, and DD genotypes (n = 36, 34, and 12, respectively). The acute responses of PRA and blood pressure to an ACE inhibitor were similar in the three groups. The blood pressure response was negatively correlated with baseline PRA (r = 0.497). These data suggest that PRA but not the I/D polymorphism of the ACE gene is a useful predictor of the short-term antihypertensive effects of ACE inhibitors.

Angiotensinogen and angiotensin-I converting enzyme gene polymorphisms and the risk of coronary artery disease in Chinese.

The homozygous deletion allele (DD) of the angiotensin-I converting enzyme (ACE) gene and the T235 homozygote of the angiotensinogen (AGT) gene have been reported to be correlated with an increased prevalence of coronary artery disease (CAD) and myocardial infarction (MI). The importance of the DD genotype and T235 homozygote as genetic risk factors for CAD in Chinese remains uncertain. This study included 426 patients who underwent coronary angiography and 180 healthy subjects without clinical evidence of CAD. Coronary angiography identified 268 patients with CAD (CAD group) and 158 patients without CAD. The healthy subjects and patients without angiographic evidence of CAD constituted the control group. Three polymorphisms were studied: an insertion/deletion (I/D) polymorphism of the ACE gene and the T174 M and M235T polymorphisms of the AGT gene. No association was found between any of the three studied polymorphisms and the risk of CAD or MI in Chinese using univariate or multivariate analysis. In multivariate analysis, the relative risks were 1.20 (95% confidence interval = 0.91-1.61, P = 0.20) for the DD genotype, 1.05 (95% CI = 0.82-1.35, P = 0.69) for the T174 homozygote, and 1.19 (95% CI = 0.91-1.55, P = 0.20) for the T235 homozygote. Similarly, no significant difference was found in the frequencies of the DD genotype and the T174 and T235 homozygotes between the control group, the CAD group, the non-MI group, and the MI group when analyzed according to sex, age, or degree of risk. Our data suggest that neither the DD genotype of the ACE I/D polymorphism nor the T174 and T235 homozygotes of the AGT gene confer significant risk for CAD or MI in Chinese.

The deletion polymorphism of the angiotensin I-converting enzyme gene is associated with target organ damage in essential hypertension.

The activity of the renin-angiotensin-aldosterone system is thought to play a significant role in the development of target organ damage in essential hypertension. An insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene has recently been associated with increased risk for left ventricular hypertrophy and coronary heart disease in the general population. The D allele is associated with higher levels of circulating ACE and therefore may predispose to cardiovascular damage. The study presented here was performed to investigate the association between the ACE genotype, microalbuminuria, retinopathy, and left ventricular hypertrophy in 106 patients with essential hypertension. ACE gene polymorphism was determined by polymerase chain reaction technique. Microalbuminuria was evaluated as albumin-to-creatinine ratio (A/C) in three nonconsecutive first morning urine samples (negative urine culture) after a 4-wk washout period. Microalbuminuria was defined as A/C between 2.38 to 19 (men) and 2.96 to 20 (women). Hypertensive retinopathy was evaluated by direct funduscopic examination (keith-Wagener-Barker classification) and left ventricular hypertrophy by M-B mode echocardiography. The distribution of the DD, ID, and II genotypes was 27, 50, and 23%, respectively. The prevalence of microalbuminuria, retinopathy, and left ventricular hypertrophy was 19, 74, and 72% respectively. There were no differences among the three genotypes for age, known duration of disease, body mass index, blood pressure, serum glucose, uric acid, and lipid profile. DD and ID genotypes were significantly associated with the presence of microalbuminuria (odds ratio, 8.51; 95% confidence interval, 1.07 to 67.85; P = 0.019), retinopathy (odds ratio, 5.19; 95% confidence interval, 1.71 to 15.75; P = 0.005) and left ventricular hypertrophy (odds ratio, 5.22; 95% confidence interval, 1.52 to 17.94; P = 0.016). Furthermore, patients with DD and ID genotypes showed higher levels of A/C (3.6 +/- 0.9, DD; 2.6 +/- 0.7, ID; 0.9 +/- 0.2 mg/mmol, II; P = 0.0015 by analysis of variance) and increased left ventricular mass index (152 +/- 4.7, DD + ID versus 133 +/- 5.7 g/m2, II; P = 0.01) compared with II patients. The D allele was significantly more frequent in patients with microalbuminuria (odds ratio, 2.59; 95% confidence interval, 1.24 to 5.41; P = 0.013) and in those with retinopathy (odds ratio, 2.44; 95% confidence interval, 1.21 to 4.90; P = 0.015). Multiple regression analyses performed among the entire cohort of patients demonstrated that ACE genotype significantly and independently influences the presence of retinopathy, left ventricular hypertrophy, and microalbuminuria. In conclusion, the D allele of the ACE gene is associated with microalbuminuria as well as with retinopathy and left ventricular hypertrophy, and seems to be an independent risk factor for target organ damage in essential hypertension.

The role of angiotensin I-converting enzyme gene polymorphism in renal disease.

Some renal diseases (e.g. diabetic nephropathy and IgA glomerulonephritis) cluster within families, consistent with a strong genetic component for the development or progression of these diseases, or both. In this context it is attractive to examine the insertion/deletion polymorphism of the angiotensin I-converting enzyme. This polymorphism determines the concentration of angiotensin I-converting enzyme not only in serum, but also in tissues and thereby presumably the locally available concentration of angiotensin II. Several studies have examined whether this polymorphism is associated with the development of diabetic nephropathy, but most of these failed to show such an association. Studies in patients suffering from IgA glomerulonephritis or other renal diseases, including diabetic nephropathy, demonstrated that the insertion/ deletion polymorphism plays a role in the progression of renal diseases and in the response to treatment with angiotensin I-converting enzyme inhibitor.

Deletion Polymorphism of the Angiotensin I‐Converting Enzyme Gene Associates with Increased Risk for Late Potentials in Patients with Myocardial Infarction

Background: The pathogenesis of the occurrence of late potentials (LP) has not been fully elucidated. Deletion polymorphism in the Angiotensin I‐converting enzyme (ACE) gene may relate the myocarclial remodeling after the myocardial infarction (Ml). The purpose of this study was to evaluate the significance of ACE gene polymorphism for the occurrence of LPs after Ml.Methods: A 287 base pair (bp) insertion/deletion polymorphism in intron 16 of the ACE gene was determined by polymerase chain reaction and LPs were also examined by signal‐averaged EGC in 136 patients with Ml. Polymorphism of the ACE gene was characterized by three genotypes: II, ID, and DD. Signal‐averaged ECG were recorded using X, Y, Z leads and LP were defined by time‐domain analysis as low amplitude potentials exceeding 20 ms after the QRS‐end and filtered QRS &gt;115 ms.Results: Positive LPs were noted in 40 of 136 patients with Ml. No differences could be detected between patients with LP‐positive and LP‐negative for the location of Ml, the success rate of reperfusion therapy, and left ventricular end‐diastolic volume (126 ± 40 vs 113 ± 43 mL/m2). In patients with LP‐positive compared with those in LP‐negative, filtered QRS was significantly higher (135 ± 8 vs 107 ± 8 ms), left ventricular ejection fraction was lower (47 ± 12 vs 54%± 11 %), and peak was higher (3602 ± 2928 vs 2614 ± 2360 IU/L). The frequency of ACE/DD genotype was associated with patients with LP‐positive (18 of DD, 18 of ID, and 4 of II for patients with LP‐positive, while 25 of DD, 42 of ID, and 29 of II for patients with LP‐negative). In the study population, the ACE / DD genotype was associated with patients with LP‐positive when compared with the ACE ID &amp; II genotype (x2= 4.7, P = 0.03).Conclusion: ACE/DD genotype of the ACE gene may be associated with the occurrence of LP after Ml.

Significance of angiotensin I-converting enzyme and angiotensin II type 1 receptor gene polymorphisms as risk factors for coronary heart disease

The D allele of an insertion/deletion ( I D ) polymorphism in the angiotensin I-converting enzyme (ACE) gene is associated with a risk of myocardial infarction, and the relative risk associated with the ACE D allele is increased by the C allele of an angiotensin II type 1 receptor (AT 1R) gene polymorphism (an A → C transversion at nucleotide position 1166) [28]. The relation of the ACE and AT 1R gene polymorphisms to coronary heart disease and the severity of coronary artery stenosis has now been investigated in 133 patients with myocardial infarction (MI) or angina pectoris who underwent coronary angiography and in 258 control subjects. The frequency of the ACE DD genotype as compared with non- DD was significantly higher in the patients who experienced an MI and in the low-risk patients than that in the controls ( P < 0.05). The DD genotype showed a significantly increased risk of MI (odds ratio 1.85). The frequency of the AT 1R A C genotypes did not differ between the patients and the controls. The severity of coronary stenosis in the patients was estimated by the number of affected vessels (> 75% stenosis) and the coronary score of Gensini. Neither the number of affected vessels nor the coronary score differed among the ACE I D genotypes. However, the number of affected vessels was significantly greater in patients with the AT 1R AC genotype than in those with the AA genotype (1.93 ± 0.27 vs. 1.27 ± 0.99; P < 0.05) ( CC genotype was not found in the patients). After excluding patients with diabetes mellitus, the coronary score of those with the AC genotype was also significantly higher than in those with the AA genotype (51.7 ± 34.4 vs. 18.2 ± 23.3; P < 0.01). These results suggest that the ACE D allele is associated with the occurrence of myocardial infarction, while the AT 1R C allele is involved in the development of the coronary artery stenosis.

Deletion polymorphism in the angiotensin I converting enzyme (ACE) gene as a genetic risk factor for sarcoidosis.

Genetic control of serum angiotensin I converting enzyme (SACE) levels has been suggested. A study was undertaken to elucidate the role of this polymorphism in sarcoidosis. Three hundred and forty one unrelated healthy controls and 103 consecutive patients with sarcoidosis participated in the study. SACE levels and an insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene were studied in each subject and new reference intervals for SACE activity for each genotype were determined. The difference in genotype and allele frequencies between controls and patients was analysed and odds ratios were calculated to estimate the relative risk. A significant association was seen between ACE gene polymorphism and SACE levels in both patients and controls. The new reference intervals for each genotype discriminated abnormal SACE levels in patients more accurately, especially those with genotype II. In women the frequencies of allele I were 0.68 (allele D 0.32) in controls and 0.58 (allele D 0.42) in patients, and the difference between the two female groups was significant (p < 0.05). Thus, an excess of genotype ID or DD was observed in female patients (odds ratio 2.18; 95% confidence interval 1.18 to 4.01; p = 0.01). These findings suggest that ACE gene polymorphism is associated with SACE levels in both patients with sarcoidosis and controls. ACE gene polymorphism should be further evaluated as a candidate marker for an increased risk of sarcoidosis.

Relationships between angiotensin I converting enzyme gene polymorphism and renal complications in Korean IDDM patients.

ObjectivesThe prognosis of IDDM is mainly dependent on complicated diabetic nephropathy which is probably determined by both metabolic abnormalities and genetic predisposition. Angiotensin I converting enzyme (ACE) regulates systemic and renal circulations through angiotensin II formation and kinins metabolism. The insertion(I)/deletion(D) polymorphism in intron 16 of ACE gene is strongly associated with ACE levels, and subjects homozygote for deletion (genotype DD) have the highest plasma values. Recently, it was reported that I/D polymorphism of ACE gene is associated with diabetic nephropathy in Caucasian IDDM patients. We studied the relationship between the ACE gene polymorphism and diabetic nephropathy in Korean IDDM patients.MethodsThe study population consisted of 59 IDDM patients (duration> 5yrs) and 107 control subjects. IDDM subjects were divided into 2 groups according to the presence or absence of diabetic nephropathy (with nephropathy: n=31, without nephropathy: n=28). After extraction of genomic DNA from peripheral blood leukocytes, PCR was performed using the sense primer (5′-GCC CTG CAG GTG TCT GCA GC-3′) and anti-sense primer (3′-TGC CCA TAA CAG TGC TTC ATA-5′), respectively. The PCR products were electrophoresed in 2% agarose gels, and DNA was visualized directly with ethidium bromide staining.ResultsFrequencies for II, ID and DD genotypes were similar in IDDM subjects and controls (23:19:17 vs 49:41:17, p=0.142) and derived allele frequencies for I and D alleles were similar in both groups (0.551:0.449 vs 0.649:0.351, p=0.098). The ACE genotype distributions were not different in diabetic subjects with or without nephropathy (12:9:10 vs 11:10:7, p=0.78) and derived allele frequencies were also similar (0.532:0.468 vs 0.571:0.429, p=0.81).ConclusionThe I and D allele frequency in our controls was different compared to ACE allele frequencies of Caucasian populations, but very similar compared to those of Chinese or Japanese subjects. We found that I/D polymorphism of ACE gene is not implicated in the diabetic nephropathy of Korean IDDM patients and may be explained by ethnic differences.