Angiotensin-converting enzyme inhibitors in the treatment of sarcoidosis and association with ACE gene polymorphism: Case series.

Angiotensin-converting enzyme (ACE) is used as a marker for sarcoid disease activity.1 We present an observational study of four African-American patients all of whom demonstrated improvement in their sarcoidosis after treatment with ACE inhibitors for hypertension.

Angiotensin I-converting enzyme gene polymorphism and diabetic nephropathy in Filipino type 2 diabetes mellitus patients / Journal of the ASEAN Federation of Endocrine Societies

Objective. Previous studies have demonstrated the role of genetic susceptibility in the pathogenesis of diabetic nephropathy. The study aimed to determine the frequencies of angiotensin I-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in a pilot population of Filipino type 2 diabetic patients and normal controls. Methods. An analysis of the ACE gene polymorphism was performed in 42 diabetic patients with and without nephropathy, and 24 normal controls. The analysis was done using polymerase chain reaction, restriction enzyme digestion, and gel electrophoresis techniques to determine the polymorphism (II, DD or ID). Independent T-tests and chi-square tests were used to compare clinical characteristics, and logistic regression analysis was done to determine odds ratio for development of nephropathy. Results. The ID polymorphism of the ACE gene was more frequent (52.4%) in patients with diabetic nephropathy (n=21). In those without nephropathy (n=21), II was more common (61.9%). ID was the more frequent genotype in the normal controls (n=24) (58.3%). The odds of developing diabetic nephropathy were increased by 4.8 times in those with ID polymorphism, and 2.9 times in those with DD. Conclusion. The D allele was more common in patients with diabetic nephropathy, similar to the observation in South Indian patients. Since the study involved only a small pilot group, studies on a larger population is needed to establish the hypothesized role of the D allele in susceptibility to diabetic nephropathy in Filipinos.

Angiotensina-(1-9) disminuye el remodelamiento cardiovascular hipertensivo independiente de los niveles de ECA y de angiotensina II / Angiotensin-(1-) reduces hypertensive cardiovascular remodeling independent of ACE and Ang II levels

Resumen: La enzima convertidora de angiotensina I (ECA2) a través de Angiotensina (Ang)-(1-9) más que Ang-(1-7) contrarresta los efectos deletéreos de ECA y Ang II. Se desconoce si Ang-(1-9) es efectiva en el tratamiento del remodelamiento cardiovascular (RMCV) hipertensivo, en ratas con polimorfismo del gen de la ECA. Objetivo: Determinar el efecto de Ang-(1-9) en el tratamiento del RMCV hipertensivo en ratas con niveles genéticamente determinados de ECA y Ang II. Métodos: Ratas normotensas homocigotas, Lewis (LL) y Brown Norway (BN), se les indujo HTA a través del modelo Goldblatt (GB, 2 riñones-1 pinzado). Después de 4 semanas, las ratas hipertensas se rando-mizaron para recibir Ang-(1-9) (602 ng/Kg min) o una coadministración de Ang-(1-9)+A779 (100 ng/Kg min, antagonista del receptor MAS de Ang-(1-7)) durante 14 días mediante una minibomba. Como controles se usaron ratas sometidas a operación ficticia (Sham). Se determinó masa corporal (MC), presión arterial sistólica (PAS), masa ventricular (MV), área de cardiomiocitos (AC), área y grosor de la túnica media (ATM, GTM), fracción volumétrica de colágeno total (FVCT) en el ventrículo izquierdo (VI), niveles proteicos de colágeno tipo I (Col I) en la aorta (Ao) y la infiltración de macrófagos en Ao y VI, por medio de su molécula especifica ED1 (ED1-Ao, ED1-VI). Resultados: La administración de Ang-(1-9) disminuyó significativamente PAS, MV, AC, FVCT, Col I, ATM, GTM, ED1-Ao (-) y ED1-VI, en las ratas hipertensas LL y BN respecto a las ratas GB sin tratamiento, respectivamente. Este efecto no fue inhibido por el antagonista A779. El polimorfismo de la ECA no modificó la respuesta al tratamiento. Conclusión: Ang-(1-9) redujo eficazmente la HTA y el RMCV secundario, independiente al polimorfismo en el gen de la ECA. Este efecto posiblemente es directo ya que no fue mediado por Ang-(1-7). Fondecyt 1100874.

Background: The angiotensin I converting enzyme 2 (ACE2) counteracts the deleterious effects of ACE and Ang II through angiotensin (Ang) -(1-9) rather than Ang-(1-7). In addition, it is not clear whether Ang-(1-9) is effective in the reversal of hypertensive cardiovascular remodeling (CVRM) in rats with ACE gene polymorphism. Objective: To determine the effect of Ang-(1-9) in the prevention of hypertensive CVRM in rats with genetically determined levels of ACE and Ang II. Methods: In normotensive homozygous Lewis (LL) and Brown Norway (BN) rats hypertension was induced by the Goldblatt 2 kidney-1 pinch model. After 4 weeks, rats were randomized to receive Ang- (1-9) (602 ng / Kg min) or the co administration of Ang- (19) + A779 (100 ng / kg min, a MAS receptor antagonist of Ang- (1-7)) for 14 days. Sham operated rats were used as controls. We determined body mass (BM), systolic blood pressure (SBP), ventricular mass (VM), cardiomyocyte area (CA), area and thickness of the aortic media (ATM, TTM), LV total collagen volume fraction (FVCT), type I collagen protein levels (Col I) in the aorta (Ao) and macrophage infiltration in LV and Ao, through its specific molecule ED1 (ED1-Ao, ED1-VI). Results: Continuous administration of Ang- (1-9) significantly decreased SBP, VM, CA, TCVF, Col I, TTM, and ED1 in the aorta and left ventricle of hypertensive rats. This effect was not inhibited by the antagonist A779. ACE polymorphism did not modify the response to treatment. Conclusion: Ang- (1-9) effectively reduced hypertension induced CVRM independent of ACE gene polymorphism. This effect was not mediated by Ang- (1-7).

Genetic and Environmental Factors that Influence on Erythropoietin Resistance in Patients on Hemodialysis / 대한신장학회잡지

BACKGROUND: Erythropoietin (EPO) requirement to reach a specified target hemoglobin level varies in patients on dialysis, the reasons being multifactorial. Angiotensin II has been shown to stimulate proliferation of early erythroid progenitors via erythropoietin and the plasma level of angiotensin II has been strongly associated with angiotensin converting enzyme (ACE) gene polymorphism. EPO resistance index (ERI, weekly rhEPO dose/hematocrit/body weight) is a collective responsiveness between EPO and hematocrit. We have evaluated whether ACE gene polymorphism might exert effect on ERI and also have analysed various laboratory parameters that could affect erythropoietin requirement in HD patients. METHODS: We have compared various demographic data and laboratory parameters, including age, sex, months on dialysis, body mass index (BMI), EPO requirement, ERI, high sensitivity C-reactive protein (hsCRP), ferritin, albumin, hematocrit, iPTH, Kt/V, normalized protein catabolic rate (nPCR), cause of renal failure and whether or not patients were on ACE inhibitor or Angiotensin receptor blocker (ARB), in 199 patients on hemodialysis therapy [M: F 94: 105, Age 61+/-13, duration of dialysis 63 (3-287 months)] according to ACE gene polymorphism (II, ID, DD). We also have assessed independent association of ERI with demographic variables and laboratory parameters using linear regression analysis. RESULTS: There was statistically significant difference (p=0.034) in ERI in the II/ID group compared to the DD group and it was lower in the DD group. But there was no statistically significant difference in other demographic data and laboratory parameters according to ACE gene polymorphism. In the linear regression analysis, lower BMI (p<0.001), female gender (p=0.001), and ACE gene polymorphism (non-DD vs. DD, p=0.027) were determined to be independent factors affecting high ERI. CONCLUSION: ACE gene polymorphism could be determining factor of EPO requirement in patients on hemodialysis. Improving nutritional status might be helpful in reducing EPO requirement and we should consider the gender difference in determining EPO dose in patients on hemodialysis.

Risk Factors for Atrophic Renal Scar

PURPOSE: An atrophic renal scar(RS) is one of the underlying causes for childhood hypertension and chronic renal failure. The risk factors for atrophic renal scar were evaluated. METHODS: 41 children, who presented with first febrile urinary tract infection at the Ewha Womans University Hospital between 1995 and 2003 and had generalized atrophic RS on 99mTc-DMSA renal scan, were retrospectively studied. Atrophic RS was divided into severe atrophic RS(n=14) if relative uptake on renal scan was below 10%, or mild atrophic RS(n= 27) if relative uptake on renal scan was between 10-35%. RS was defined as congenital if the scar was detected on the first renal scan, and as acquired if the scar developed on the follow-up renal scan from acute pyelonephritis of the first renal scan. The control group was consisted of randomly selected 41 children with segmental RS. The risk factors for atrophic RS such as the generation time, VUR, gender and ACE gene polymorphism were evaluated. RESULTS: The age distribution of atrophic RS and segmental RS did not differ significantly (P>0.05). The rate of congenital RS in atrophic RS was 61.0%(25/41), which was significantly higher than 9.8%(4/41) of segmental RS(P0.05). But in children with VUR, there was a higher proportion of males with severe atrophic RS than segmental RS(85.7%:45.5%). ACE gene polymorphism did not differ between the atrophic and segmental RS groups, irrespective of the presence of VUR(P>0.05). CONCLUSION: Most atrophic RSs were congenital which could not be preventable postnatally and the major risk factors were VUR and the male gender. ACE gene polymorphism was not the significant risk factor for an atrophic RS.

Polymorphism of the ACE Gene in Dialysis Patients: Overexpression of DD Genotype in Type 2 Diabetic End-Stage Renal Failure Patients

The angiotensin-converting enzyme (ACE) gene DD homozygote has been suggested to be a significant risk factor for the progression of diabetic nephropathy. We analyzed clinical parameters and ACE genotype distribution between type 2 diabetic patients at the extremes of renal risk, i.e. an end-stage renal failure (ESRF) group (n = 103, group 1) who were on dialysis therapy due to progression of diabetic nephropathy, and a no progression group (n = 88, group 2) who had maintained normal renal function and normoalbuminuria for more than 15 years. There were no significant differences in age, sex, body mass index, HbA1c level, or lipid profiles between the two groups (p > 0.05). Group 1 had a significantly higher prevalence of hypertension [group 1: 82.5% (85/103) vs. group 2: 50.0% (44/88), p < 0.05] and diabetic retinopathy [group 1: 103/103 (100%) vs. group 2: 28/88 (31.8%), p < 0.05] than group 2. Daily urinary albumin excretion was also higher in group 1 than in group 2 [group 1: 2873 +/- 2176 mg/day vs. 12 +/- 7 g/day, p < 0.05]. The frequencies of the DD, ID, and II genotypes of the ACE gene in group 1 and group 2 were 26.2%, 47.6%, and 26.2%, and 7.9%, 57.9%, and 34.2%, respectively. The ACE genotype frequencies between the two groups were significantly different according to a chi-square test with Bonferroni's correction (p = 0.004). The presence of the DD genotype increased the risk of ESRF 4.286-fold compared to the II genotype [odds ratio 4.286, 95% CI 1.60- 11.42, p = 0.005]. The frequency of the D-allele was higher in both male and female patients in group 1 compared to group 2, but reached statistical significance only in males [male, group 1: 50.8% vs. group 2: 35.0%, p = 0.018, female, group 1: 48.8% vs. group 2: 39.5%, p = 0.231]. This study, although limited by sample size, showed that type 2 diabetic ESRF patients more frequently expressed the DD genotype. These findings may substantiate the previously noted relationship between the ACE DD genotype and the progression of diabetic nephropathy in Korean type 2 diabetic patients.

Angiotensin Converting Enzyme Gene Polymorphism in Alport Syndrome

PURPOSE: Alport syndrome is clinically characterized by hereditary progressive nephritis causing ESRD with irregular thickening of the GBM and sensory neural hearing loss. The mutations of type IV collagen gene(COL4A5) located on the long arm of X chromosome is considered responsible for most of the structural abnormalities in the GBM of Alport patients. Since no definite clinical prognostic predictor has been reported in the disease yet, we designed this study to evaluate the significance of genetic polymorphism of the angiotensin converting enzyme in children with Alport syndrome as a prognostic factor for disease progression. METHODS: ACE I/D genotype were examined by PCR amplification of the genomic DNA in 12 patients with Alport syndrome and 12 of their family members. Alport patients were divided into two groups; the conservative group, those who had preserved renal function for more than 10 years of age, the early CRF group, those who had progressed to CRF within 10 years of age. RESULTS: The mean age of onset was 3.45+/-2.4 years in the conservative group, 4.4+/-1.2 years in the early CRF group. Sex ratios were 5:3 and 2:1 in each group. Among 12 cases of patients, 4 cases were in early CRF group and their mean duration of onset to CRF was 4.5 years(8.9 years of age). Eight patients(67%) were in the conservative group and they had normal renal function for more than 10 years of age(mean duration of renal preservation was 10.6 years). The incidence of II type ACE gene were in 25.0%(3 cases), ID type in 41.7 %(5 cases), DD type in 33.3%(4 cases). There was no significant difference between Alport patient and normal control(II type 44.3%, ID type 40.9%, DD type 14.8%). The incidence of DD type of early CRF group were higher than that of the conservative group(75% vs 12.5 %)(p<0.05). There was no difference in ACE gene polymorphism between normal Alport family members and control group. CONCLUSION: Even though there was no significant difference of ACE polymorphism between Alport patients and the normal control group, the incidence of DD type is significantly increased in early CRF group which means DD type of ACE polymorphism has a possibility of being a predictor for early progression to CRF in Alport patients.

Polymorphism of angiotensin I converting enzyme (ACE) gene according to the severity of asthma in Korean adult asthmatics / 천식및알레르기

BACKGROUND AND OBJECTIVE: Many chemical mediators such as histamine, prostaglandins, leukotrienes, bradykinin, angiotensisn II (A II), and even angiotensin converting enzyme (ACE) affect the pathophysiology of asthma. ACE exists in the epithelium, endothelium, neuroepithelium, plasma, and especially in high concentrations in human lung tissue. ACE converts A I to A II, which is highly vasoconstrictive, bronchoconstrictive, inflammatory substance, and can also inactivate bradykinin. ACE polymorphism determines the level of ACE such as DD, higher concentration of ACE, but II, lowest concentration of that, so in DD type, the level of A II increase, but that of bradykinin decrease. From that point we can speculate polymorphism of ACE gene anyhow affects asthma, so we carried out this study for evaluating relationships between the ACE genotype distribution and genesis and severity of asthma in Korean adult asthmatics. MATERIALS AND METHODS: The study population consisted of 150 asthmatics, 57 patients of non asthmatic lung diseases including lung cancer (n=10), pulmonary tuberculosis (n=27), empyema (n=3), pneumonia (n=11), bronchiectasis (n=5) and lung abscess (n=1) and 100 normal healthy subjects without hypertension, cardiovascular disease, diabetes mellitus and nephropathy which may bias the result. Bronchial asthmatics were classified into 3 groups according to the criteria of the NAPE. PCR (polymerase chain reaction) for ACE genotypes was performed. PCR products were electrophoresed in 1% agarose gels, and then DNA pattern was directly visualized under ethidium bromide staining. RESULTS: The frequency for II, ID, and DD genotypes were 46 (46%), 38 (38%), 16 (16%) in control group, 59 (39.6%), 74 (49.5%), 17 (10.9%) in asthma group and 28 (49.1%), 24 (42.1%), 5 (8.8%) in non-bronchial lung disease group, respectively. There was no signi- ficant difference in frequency of ACE genotype distribution among the 3 groups (p > 0.05). The frequency for II, ID, and DD genotypes in the 3 groups of asthmatics were 17 (34%), 27 (54%), 6 (12%) in mild subset, 13 (26%), 30 (60%), 7 (14%) in moderate subset, and 11 (22%), 33 (66%), 6 (12%) in severe subset. Even though there was also no significant difference among the 3 severity subsets in the asthma group, the frequency of non-DD subsets such as II and ID was higher in moderate and severe asthmatics. CONCLUSION: The results suggest that ACE gene polymorphism dose not affect the genesis but can progress asthma in Korean adult asthmatics. However, further mass studies on asthmatics will be needed to clarify the effect of ACE polymorphism on the severity of Korean adult asthmatics.

Correlation Between Angiotensin-Converting Enzyme(ACE) Inhibitor Induced Dry Cough and ACE Gene Insertion/Deletion(I/D) Polymorphism / 결핵

BACKGROUND: Persistent nonproductive cough is a major adverse effect encountered with ACE inhibitor treatment and the most frequent reason for withdrawal of the drug. The mechanism of cough was postulated to be associated with accumulation of bronchial irritants which are substrates of ACE. It has been speculated that occurrence of this adverse effect is genetically predetermined; in particular, variants of the genes encoding ACE. To investigate this relationship, we determined ACE gene Insertion/Deletion polymorphism in subjects with and without a history of ACE inhibitor-induced cough. METHODS: Among the 339 patients with ACE inhibitor treatment, subjects who developed cough that resolved when not taking medication were designated to cough group and other subjects who did not complain cough were designated to non-cough group. Clinical characteristics of the patients were collected by review of medical records. ACE genotypes were determined by PCR amplification of DNA from peripheral blood RESULTS: 37 patients complained of dry cough(cough group) and 302 patients did not complained of cough(non-cough group). The incidence of ACE inhibitor induced dry cough was 10.9%. There was a preponderance of females in the cough group (M:F=24.3%:75.7%) compared to the non-cough group(M:F=49.7%:50.3%, p=0.004). There was no significant difference in mean age, underlying diseases, and kinds and frequencies of ACE inhibitors and their mean dosage between the both groups. ACE genotypic frequencies were I/I : I/D : D/D = 16.2%:18.9%:64.9% in the cough group and 18.9%:18.2%:62.9% in the non-cough group which showed no significant difference between the both groups(p=0.926). Allelic frequencies were I : D = 25.7%:74.3% and 28.0%:72.0% in the cough and non-cough group respectively and the difference was not significant(p=0.676). CONCLUSION: The incidence of ACE inhibitor-induced cough are 10.9%, and women are more susceptible to ACE inhibitor-induce cough. ACE inhibitor induce dry cough is not associated with ACE gene Insertion/Deletion polymorphism.

Association between ACE Gene Polymorphism and Nephropathy in NIDDM Patients / 대한신장학회잡지

It has been reported that the genetic susceptibility may be an important factor in the development of nephropathy in diabetic patients, and the genetic polymorphism of angiotensin-converting enzyme (ACE) has been extensively studied for its possible role. The ACE affects the cardiovascular system through angiotensin II formation and inactivation of bradykinin. The 21 kilobases-long ACE gene located on the long arm of chromosome 17 is composed of 26 exons and 25 introns. The presence/absence of a 287 base pairs fragment in the 16th intron of the ACE gene determines its genotype either as insertion(I) or deletion(D). These genotypes in turn are used to characterize the polymorphism as II, ID or DD type. Each of these genotypes has been reported to show different activity of serum ACE. Recent reports have suggested that genotype DD or D allele may be involved in the nephropathy in diabetics while genotype II may lower the chance for diabetic nephropathy. The present study investigates the effects of genetic polymorphism of ACE on the nephropathy in NIDDM by assessing ACE genotypes and activities on 148 NIDDM patients who have been diagnosed at least 10 years prior to the study, as well as 146 normal controls. The NIDDM group is composed of 70 patients with nephropathy and 78 without nephropathy. The results were as follows. 1) In the diabetic group, the absence/presence of nephropathy showed no significant difference in terms of age, gender, body mass index, HbA1C, cholesterol, triglyceride and HDL cholesterol(p>0.05). No significant differences on the clinical parameters were noted according to the ACE genotypes either(p>0.05). 2) The ratio of ACE genotypes(II:ID:DD) was 0.36:0.48:0.16 for the normal control group, 0.28:0.56: 0.16 for the NIDDM without nephropathy group, and 0.26:0.51:0.23 for the NIDDM with nephropathy group. The ratios of I and D allele were 0.60:0.40, 0.56:0.44 and 0.51:0.49, respectively. In all three groups, higher ratio I allele over D allele was noted and the ID genotype was most frequent followed by II and DD types, although the differences between the groups were not statistically significant(p>0.05). 3) In the normal controls group, ACE activities for DD, ID and II genotypes were 54.0 15.0, 40.4 12.4 and 30.1 11.8U/L, respectively, with significant difference among the genotypes. In the NIDDM without nephropathy group, there was no difference among the three genotypes(DD, ID, II; 47.2 15.1 vs. 36.6 18.7 vs. 32.0 13.4). In the NIDDM with nephropathy group, the activity for DD and ID genotypes were significantly higher than II genotype(47.7 31.0, 47.4 30.7 vs. 17.8 17.9U/L, p0.05). The results of the present study show that in the normal group genotype ID is most frequent followed by II and DD, and the I allele is more frequent than D allele. These results are similar to the reports from China and Japan, unlike the results from Europe or USA where genotype DD and D allele are more frequent than II genotype and I allele, suggesting an ethnic difference. Furthermore, the NIDDM patients group, regardless of the presence of nephropathy, showed no significant difference from the normal group in terms of ACE genotypes or allele types, suggesting lack of association between the nephropathy and the ACE gene polymorphism. The ACE activity also showed no significant relationship with various clinical parameters or complications. Further studies on the effects of ACE polymorphism and ACE activity on the progression of nephropathy may be needed.

Clinical Characteristics and Angiotensin Converting Enzyme Gene Polymorphism in the Susceptibility to Angiotensin Converting Enzyme Inhibitor-Induced Cough

BACKGROUND: Cough is a frequent side effect of angiotensin converting enzyme(ACE) inhibitors and the mechanism of cough is postulated to be associated with accumulation of bronchial irritants which are substrates of ACE. Based on this pathophysiologic mechanism, baseline ACE activity could potentially play the key role in the development of ACE inhibitor-induced cough and ACE gene polymorphism, which account for part of the ACE activity, and to compare the clinical characteristics between subjects who developed cough and those who did not with ACE inhibitor use. METHOD: The cough group(N=84) consisted of subjects who developed troublesome cough with ACE inhibiors and who ceased coughing in 4 weeks after cessation of ACE inhibitor treatment. Patients with evidence of acute respiratioy illness were excluded. The non-cough group(N=116) consisted of subjects who did not develop cough with over 12 months of ACE inhibitor treatment. Clinical characteristics were collected by personal contact and chart review. ACE genotyping was done by PCR amplification of DNA from peripheral blood using previously published primers and agarose gel electrophoresis. RESULTS: Underlying diseases of the cough group were hypertension(47), valvular heart disease(23), ischemic heart disease(4), dilated cardiomyopathy(7) and others (3), whereas Underlying diseases of the non-cough group were hypertension(48), valvular heart disease(33), ischemic heart disease(12), dilated cardiomyopathy(20) and others(3). There was no significant difference in the distribution of underlying diseases between the two groups. Cough induced by ACE inhibitors occurred in an average of 8 weeks after treatment initiation and subsided in an average of 3.8 weeks after discontinuation of ACE inhibitors. There was a preponderance of females in the cough group(F : M=73 : 27) compared to the non-cough group(F : M=40 : 60, p<0.01). There was no significant difference in mean age, total cholesterol, and the frequency of hypertension and diabetes between the two groups. Genotypic frequencies of ACE gene were I/I : I/D : D/D=38 : 42 : 30 for the cough group and 45 : 36 : 19 for the non-cough group which showed no significant difference between the two groups. Allelic frequencies were I : D=54 : 46 and 62 : 38 in the cough and non-cough group respectively and the difference was not statistically significant. CONCLUSION: Women are more susceptible to ACE inhibitor-induced cough, and ACE inhibitor induced cough is not associated with ACE gene polymorphism.

Clinical Characteristics and Angiotensin Converting Enzyme Gene Polymorphism in the Susceptibility to Angiotensin Converting Enzyme Inhibitor-Induced Cough

BACKGROUND: Cough is a frequent side effect of angiotensin converting enzyme(ACE) inhibitors and the mechanism of cough is postulated to be associated with accumulation of bronchial irritants which are substrates of ACE. Based on this pathophysiologic mechanism, baseline ACE activity could potentially play the key role in the development of ACE inhibitor-induced cough and ACE gene polymorphism, which account for part of the ACE activity, and to compare the clinical characteristics between subjects who developed cough and those who did not with ACE inhibitor use. METHOD: The cough group(N=84) consisted of subjects who developed troublesome cough with ACE inhibiors and who ceased coughing in 4 weeks after cessation of ACE inhibitor treatment. Patients with evidence of acute respiratioy illness were excluded. The non-cough group(N=116) consisted of subjects who did not develop cough with over 12 months of ACE inhibitor treatment. Clinical characteristics were collected by personal contact and chart review. ACE genotyping was done by PCR amplification of DNA from peripheral blood using previously published primers and agarose gel electrophoresis. RESULTS: Underlying diseases of the cough group were hypertension(47), valvular heart disease(23), ischemic heart disease(4), dilated cardiomyopathy(7) and others (3), whereas Underlying diseases of the non-cough group were hypertension(48), valvular heart disease(33), ischemic heart disease(12), dilated cardiomyopathy(20) and others(3). There was no significant difference in the distribution of underlying diseases between the two groups. Cough induced by ACE inhibitors occurred in an average of 8 weeks after treatment initiation and subsided in an average of 3.8 weeks after discontinuation of ACE inhibitors. There was a preponderance of females in the cough group(F : M=73 : 27) compared to the non-cough group(F : M=40 : 60, p<0.01). There was no significant difference in mean age, total cholesterol, and the frequency of hypertension and diabetes between the two groups. Genotypic frequencies of ACE gene were I/I : I/D : D/D=38 : 42 : 30 for the cough group and 45 : 36 : 19 for the non-cough group which showed no significant difference between the two groups. Allelic frequencies were I : D=54 : 46 and 62 : 38 in the cough and non-cough group respectively and the difference was not statistically significant. CONCLUSION: Women are more susceptible to ACE inhibitor-induced cough, and ACE inhibitor induced cough is not associated with ACE gene polymorphism.