Frequency of angiotensin-converting enzyme gene polymorphism in Turkish type 2 diabetic patients

We aimed to investigate the angiotensin-converting enzyme (ACE) gene polymorphism, ACE activity and their associations with diabetic complications in Turkish patients with type 2 diabetes mellitus. A total of 143 patients and 133 controls were screened for ACE gene I/D polymorphism by using polymerase chain reaction. Serum ACE activities were determined spectrophotometrically. There was no significant difference in the distribution of ACE I/D genotypes between patients and controls. The patients with DD genotype had a higher ACE activity than those with ID and II. Hypertensive diabetic patients with DD genotype had higher ACE activities than those with ID and II. There was no significant difference in the distribution of ACE I/D genotypes between patients with and without nephropathy, retinopathy and hypertension except for patients with and without neuropathy. In patients with DD genotype, creatinine clearance correlated with duration of diabetes. The grade of retinopathy was correlated with duration of diabetes in DD and ID genotypes. The highest ACE activity was measured in hypertensive diabetics with DD genotype. ID genotype was suggested to be a risk factor and II was suggested to be protective for diabetic neuropathy. The DD and ID genotypes might be a predictor for the development of retinopathy in relation to duration of diabetes.     

ACE gene insertion/deletion polymorphism associated with 1998 World Health Organization definition of metabolic syndrome in Chinese type 2 diabetic patients

OBJECTIVE: Because ACE insertion/deletion (I/D) polymorphism has been shown to be associated with diabetes, hypertension, coronary artery diseases, and diabetic nephropathy, and because plasma ACE concentration has been found to be associated with plasma triglyceride and total cholesterol levels in patients with type 2 diabetes, the goal of this study was to investigate whether ACE gene I/D polymorphism is associated with metabolic syndrome in Chinese subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 711 patients with type 2 diabetes and 750 control subjects were studied. The ACE I/D polymorphism was determined by PCR. The definition and criteria of metabolic syndrome used in this study matched those proposed in the 1998 World Health Organization classification. RESULTS: Of 711 patients with type 2 diabetes, 534 (75.1%) fulfilled the criteria for metabolic syndrome. The prevalence of metabolic syndrome in control subjects with II, ID, and DD genotype was 9.4, 11.5, and 15.4%, respectively, and in patients with type 2 diabetes, it was 68.6, 79.2, and 86.1%, respectively. The ACE I/D polymorphism was significantly associated with the syndrome in patients with type 2 diabetes (P = 0.001). When pooling the control subjects with diabetic patients, the prevalence of metabolic syndrome in the whole study group with II, ID, and DD genotype was 37.9, 44.5, and 51.0%, respectively, and ACE I/D polymorphism was still significantly associated with metabolic syndrome (P = 0.003). Diabetic patients with DD genotype were also found to have a higher prevalence of dyslipidemia (II/ID/DD = 43.1/53.1/65.8%, P < 0.001) and albuminuria (36.0/44.6/50.6%, P = 0.018) and to have higher serum triglyceride levels (II, ID, and DD = 155 +/- 114, 170 +/- 140, and 199 +/- 132 mg/dl, respectively, P < 0.05). Control subjects with DD genotype were also found to have a higher prevalence of albuminuria or more advanced nephropathy (II/ID/DD = 5.7/14.0/15.4%, P = 0.001), whereas the prevalence of dyslipidemia was not found to be statistically different in the control group. When pooling control with diabetic subjects, ACE genotype could still be significantly associated with dyslipidemia (II/ID/DD = 34.7/41.3/52.2%, P < 0.001) and albuminuria or more advanced nephropathy (20.3/28.9/33.1%, P < 0.001). Diabetic patients with metabolic syndrome were found to have higher serum uric acid levels than those without metabolic syndrome (6.4 +/- 1.8 vs. 5.3 +/- 1.4 mg/dl, P < 0.01). CONCLUSIONS: The ACE I/D polymorphism was found to be associated with metabolic syndrome in Chinese patients with type 2 diabetes. This finding may provide genetic evidence to explain the clustering of metabolic syndrome and suggests that the renin-angiotensin system is involved in the pathophysiology of metabolic derangement in patients with type 2 diabetes.     

Angiotensin-converting enzyme genotype in blacks with diabetic nephropathy: effects on risk of diabetes and its complications.

OBJECTIVE: Among blacks, we have observed that diabetic nephropathy (DN) is a more frequent primary cause of end-stage renal disease (ESRD) in women (approximately 50%) than in men (< 20%). In this study, we consider the role of the angiotensin-converting enzyme (ACE) polymorphism in determining this gender discrepancy and its role in the course of DN. METHODS: ACE genotype (I = insertion, D = deletion) was determined in consecutive consenting patients with type 2 diabetes mellitus and DN. Charts were subsequently reviewed for renal survival and its determinants (end point: time to ESRD from first clinic visit). RESULTS: Fifty-four patients (46 blacks) who had DN and were pre-ESRD consented: II = 6, ID = 31, and DD = 17. The allele frequency for D was approximately . 61 versus .39 for the I allele and did not differ by gender. Renal disease at presentation to the renal clinic was significantly worse in II. Twenty-one patients reached ESRD (II = 4, ID = 13, DD = 4; chi2 not significant), but ACE genotype had no significant effect on renal survival. Initial serum creatinine and blood pressure over follow-up independently predicted renal survival. Among blacks reaching ESRD, the presence of the D allele was associated with higher blood pressures. Patients without a family history of diabetes (chi2, p = .01) or diabetic retinopathy (chi2, p = .02) were more likely to have the DD genotype. CONCLUSIONS: The gender discrepancy observed in rates of ESRD owing to DN in blacks is not likely dependent on ACE genotype. The effects of ACE genotype on renal disease progression were not significant; however, patients with diabetic nephropathy and DD genotype were less likely to have traditional risk factors for diabetes or diabetic nephropathy.     

Angiotensin-converting enzyme gene polymorphism and stroke in type 2 diabetic patients in Taiwan

BACKGROUND: The effect of traditional risk factors on the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and stroke was rarely studied previously. We investigated such effect in Taiwanese type 2 diabetic patients. MATERIALS AND METHODS: A total of 872 (422 men and 450 women) patients aged 63.5 (SD: 11.6) years were recruited. Among them, 92 cases (48 men and 44 women) had stroke. Polymerase chain reaction was used to classify the genotypes as II, ID and DD. Analyses were performed in separate sexes. RESULTS: The adjusted odds ratios for stroke for ID vs. II and DD vs. II were 0.837 (0.413-1.697) and 1.778 (0.596-5.300), respectively, for men; but were 1.700 (0.824-3.505) and 3.706 (1.375-9.985), respectively, for women. In models assuming recessive (DD vs. II + ID), dominant (DD + ID vs. II) and additive (II = 0, ID = 1 and DD = 2) transmission, none of the odds ratios was significant for men; but were all significant for women: 2.784 (1.137-6.818), 1.996 (1.006-3.962) and 1.877 (1.155-3.050), respectively. In models using patients without risk factors (hypertension, obesity, smoking or dyslipidaemia ) as a referent group and comparing them to patients with the risk factor and with ID/II, and with DD genotypes, all models (except for smoking) favoured an increasing trend of risk with patients having the risk factor and DD genotype at the highest risk in women. Similar trends for hypertension and dyslipidaemia were also observed in men. CONCLUSION: Traditional risk factors play an important role in the association between the ACE genotypes and stroke. Patients with DD genotype and having traditional risk factors are at the highest risk.     

ACE gene polymorphism and proliferative retinopathy in type 1 diabetes: results of a case-control study.

OBJECTIVE: To evaluate the relationship between the ACE insertion/deletion polymorphism and proliferative diabetic retinopathy in patients with type 1 diabetes of long duration. Based on epidemiological and pathophysiological findings, risk factors apart from glycemic control and duration of disease are likely to be involved in the development of proliferative retinopathy. RESEARCH DESIGN AND METHODS: In this case-control study, we compared 81 patients with longstanding (> or =20 years) type 1 diabetes who had nonproliferative (mild or moderate background) retinopathy with 95 patients with diabetes of similar duration and HbA1c who had proliferative retinopathy. To avoid the confounding effect of nephropathy, patients with overt nephropathy were excluded, and microalbuminuria was introduced into the multiple logistical regression model. The polymorphic region in intron 16 of the ACE gene (17q23) was analyzed using the polymerase chain reaction. RESULTS: The ACE genotype distribution in patients with proliferative retinopathy (DD 39.4%, ID 48.9%, II 11.7%) was significantly different (P < 0.001) from that of patients with nonproliferative retinopathy (DD 17.3%, ID 54.3%, II 28.4%). In a multiple logistical regression analysis, the adjusted relative risk for proliferative retinopathy in a patient with a DD genotype compared with a patient with an II genotype was 6.6 (95% CI 2.2-19.5), P = 0.0026. In addition to genotype, systolic blood pressure (odds ratio 1.027 [95% CI 1.0-1.1], P = 0.0093) but not microalbuminuria (< or =20 vs. > or =20 microg/min) reached statistical significance in the multiple regression model. Because subjects were matched regarding diabetes duration and HbA1c, we did not interpret the respective parameter estimates. CONCLUSIONS: These data provide evidence that deletion in the ACE gene is associated with the prevalence of proliferative retinopathy in type 1 diabetes and suggest that the DD genotype confers susceptibility to proliferative retinopathy independent of diabetic nephropathy     

Association study of the I/D polymorphism and plasma angiotensin-converting enzyme (ACE) as risk factors for stent restenosis

The ID (insertion/deletion) polymorphism of the ACE (angiotensin-converting enzyme) gene controls plasma ACE levels. Both have been correlated with ISR (in-stent restenosis) in preliminary analyses, but not confirmed in larger studies. In the present study, baseline and 6-month quantitative coronary analysis were performed in 897 patients who had stent implantation and the ID polymorphism genotyped. Plasma ACE levels were measured in 848 patients (95%). Restenosis rates among genotypes were 31.2% DD, 25.5% ID and 28.8% II (not significant). Plasma ACE levels were significantly higher in restenotic patients compared with patients without restenosis (30.7+/-18.6 units/l compared with 22.8+/-12.8 units/l; P=0.0001) and a strong independent predictor of ISR [OR (odds ratio)=3.70; 95% CI (confidence interval), 2.40-5.71; P<0.0001], except in diabetics. In the subgroup of diabetics and patients with AMI (acute myocardial infarction), the DD genotypes actually had a lower risk of ISR than the II genotypes (diabetics, OR=0.16; 95% CI, 0.04-0.69; P=0.014; and patients with AMI, OR=0.21; 95% CI, 0.061-0.749; P=0.016). After exclusion of diabetics and patients with AMI, ISR rates for genotypes in 632 patients were 31.7% DD, 24.3% ID and 17.6% II (P=0.02; DD compared with non-DD OR=1.57; 95% CI, 1.09-2.25). The association between the D allele and ISR observed in selected populations does not hold with a larger sample size. Other than sample size, clinical variables can modulate the association between ID polymorphism and ISR. Plasma ACE level is a risk factor for ISR, independently of the ID genotype.     

Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients with breast cancer and effects on prognostic factors.

The aims of the present study were to investigate the distribution of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in breast cancer patients and the association between ACE genotypes and clinicopathologic features, as well as their effects on prognosis. We assessed the I/D polymophism of the ACE gene by using polymerase chain reaction from peripheral blood in breast cancer and healthy age-matched women. The clinicopathologic parameters of breast cancer patients were obtained from medical records. Of the 57 patients, 31 (54.4%) had DD, 24 (42.1%) had ID, and 2 (3.5%) had II genotypes. In control subjects, 33 (63.5%) had DD, 12 (23.1%) had ID, and 7 (13.4%) had II genotypes. The ID genotype was seen more commonly in breast cancer patients (p = .03). When the combination of ID and II genotypes was used as a reference group, the DD genotype was associated with negative hormone receptor status (p = .003), tumor size (p = .054), and lymph node involvement (p = .07) but not histologic high grade and c-erb B2 overexpression. These results suggest that the DD genotype may accompany poor prognostic factors and influence the tumor course.     

Angiotensin-converting enzyme genotype, albuminuria and plasma fibrinogen in type 2 diabetes mellitus

AIMS: Increased fibrinogen level is considered an important atherosclerosis risk factor. Patients with type 2 diabetes frequently have increased fibrinogen levels. The aim of the present study was to examine the effect of angiotensin-converting enzyme (ACE) gene polymorphism and the effects of the diabetic environment on plasma fibrinogen in type 2 diabetes. PATIENTS AND METHODS: The study group included 125 patients with type 2 diabetes (40 men, 85 women). The average age of patients was 62 +/- 10 years. Fibrinogen concentration was determined with the thrombin coagulation test. ACE insertion/deletion (I/D) polymorphism was detected using polymerase chain reaction (PCR) assay. RESULTS: II homozygotes (n = 17) had the highest mean fibrinogen levels, ID heterozygotes (n = 75) had medium levels and DD homozygotes (n = 33) had the lowest (p = 0.054, ANOVA). II homozygotes also had significantly higher mean fibrinogen level than ID/DD carriers (4.3 +/- 1.7 vs. 3.5 +/- 1.3 g/l; p = 0.015). The indices of renal functions, i.e. albuminuria (r = 0.37; p < 0.0001) and serum creatinine (r = 0.22; p = 0.015), significantly correlated with fibrinogen levels. The correlation between albuminuria and fibrinogen was significant in the subgroups with genotypes II (r = 0.76; p = 0.001) and ID (r = 0.37, p = 0.002), whereas in the subgroup of DD homozygotes this relationship did not reach statistical significance. In the multivariate regression analysis with age, sex, BMI, creatinine, albuminuria and ACE genotype as independent variables, albuminuria was the only significant predictor of fibrinogen level (p < 0.0001). After interaction between the ACE genotype and albuminuria was included into multivariate analysis, the interaction became the only independent predictor of plasma fibrinogen level (p < 0.0001) in the model, and the model explained 25% of the plasma fibrinogen variance. CONCLUSION: ACE gene polymorphism is associated with plasma fibrinogen level in type 2 diabetes. This association is mediated by an interaction between ACE genotype and albuminuria. Diabetes patients with genotypes II or ID have increased plasma fibrinogen in the presence of albuminuria.     

I/D relationship between polymorphism of ACE gene and progression of chronic glomerulonephritis

AIM: To study prevalence of angiotensin-converting enzyme (ACE) gene polymorphism and its correlation with ACE level in Kyrgyz population suffering from chronic glomerulonephritis (CGN); to ascertain CGN progression and survival with reference to the genotype of ACE gene. MATERIAL AND METHODS: The above parameters were investigated in 76 CGN patients (mean age 34.1 +/- 1.9 years) and 48 healthy controls matched by sex and age. Amplification of the polymorphic site of the ACE gene was made with polymerase chain reaction. Spectrofluorimetry measured ACE concentration in the serum. Progression of CGN was assessed by reciprocal creatinine. Survival of the patients was calculated according to the Kaplan-Meyer method. RESULTS: The ACE genotype distribution corresponded to the Hardi-Weinberg equilibrium. However, a significant difference in the frequency of genotypes and alleles between CGN and control patients was not revealed. The activity of serum ACE in CGN and healthy subjects was noticeably higher in DD genotype than that in genotypes II and ID (P < 0.02). The former had a significantly higher level of total cholesterol and much lower glomerular filtration rate in a rapid progression of the disease estimated by reciprocal creatinine and higher 5- and 10-year survival compared to genotypes II and ID (P < 0.05). CONCLUSION: Development of CGN is not associated with any genotype of ACE gene in Kyrgyz population. At the same time, deletion polymorphism of ACE gene may serve as a predictor for CGN progression.     

Polymorphism studies of angiotensin converting enzyme gene in chronic glomerulonephritis]

AIM: To investigate the relationship between polymorphism of angiotensin-converting enzyme (ACE) gene and predisposition to chronic glomerulonephritis (CGN) as well as antihypertensive and anti proteinuric response to ACE inhibitors (ACEI) treatment, therapy with angiotensin II receptor antagonists. MATERIALS AND METHODS: Genotype was determined in 57 CGN patients and 113 subjects free of chronic diseases. Effects of ACE gene polymorphism on antihypertensive and antiproteinuric efficiency of ACEI and cozaar were studied in 35 CGN patients on monotherapy. 24-h proteinuria, levels of creatinine, potassium in the serum, arterial pressure, glomerular filtration rate were measured in all the patients. RESULTS: No significant differences were found between incidence of ACE gene genotypes and alleles in patients with CGN and controls. Maximal antihypertensive response to therapy was observed after a month treatment in patients with genotypes II and ID. Lowering of arterial pressure in patients with genotype DD was observed on month 6-12 of continuous therapy. Proteinuria diminished on the treatment month 1-3 in patients with genotypes II and ID, in genotype DD proteinuria rose for the same period of time. Proteinuria dropped similarly in all the groups by month 6-12. CONCLUSION: Relations between ACE gene polymorphism and genetic predisposition to CGN were not found. Patients with genotype II were most sensitive to IACE and cosaar treatment. Lack of an early anti proteinuric response in homozygotes DD does not determine effectiveness of long-term IACE treatment and should not be a reason for the above drug discontinuation.     

Angiotensin converting enzyme gene polymorphism and glomerular filtration rate changes in type 2 diabetic patients

It has been suggested that an insertion/deletion (I/D) polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene may be associated with diabetic nephropathy The aim of this study was to investigate whether an association exists between ACE I/D polymorphism and glomerular filtration rate (GFR) in type 2 diabetes mellitus. A total of 128 type 2 diabetic patients were included in the study with the following ACE genotype distribution: DD 40, ID 58,11 30. I/D polymorphism was determined by polymerase chain reaction (PCR). Mean GFR was not statistically different according to ACE genotype (DD: 89.9 +/- 28.1 ml/min, ID: 99.5 +/- 25.1 ml/min, II: 96.6 +/- 19.6 ml/min). There was no significant difference in genotype distribution in normo-, micro- and macroalbuminuric patients (DD:ID:II [%], normo- 35:46:19, micro-28:55:17, macro- 31:55:14). ACE I/D polymorphism does not seem to be associated with GFR in type 2 diabetic patients.     

Relationship between glomerular hyperfiltration and ACE insertion/deletion polymorphism in type 1 diabetic children and adolescents

OBJECTIVE: Glomerular hyperfiltration may predict diabetic nephropathy in type 1 diabetes, and some studies suggest that the ACE D allele is associated with diabetic nephropathy. The aim of this study was to examine a possible relationship between glomerular hyperfiltration and ACE insertion/deletion (I/D) polymorphism in type 1 diabetic children and adolescents. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted to examine the relationship between glomerular hyperfiltration and ACE (I/D) polymorphism in 76 type 1 diabetic children and adolescents without diabetic nephropathy (mean +/- SD: age 16 +/- 3 years; diabetes duration 7 +/- 4 years; age at diabetes onset 9 +/- 4 years; HbA1c 9.5 +/- 1.9%). Glomerular hyperfiltration (defined as a glomerular filtration rate [GFR] > or = 135 ml.min-1. 1.73 m-2 and by 51Cr-labeled EDTA plasma disappearance technique) and ACE I/D genotypes and plasma levels (enzyme-linked immunosorbent assay [ELISA] method) were determined. RESULTS: Of the patients, 29 (38%) displayed glomerular hyperfiltration. An association between glomerular hyperfiltration and ACE (I/D) polymorphism was observed (chi 2 = 7.09, P = 0.029) because of a reduced proportion of DD genotypes among patients with glomerular hyperfiltration (4 vs. 19; chi 2 = 6.03, P = 0.014) and not because of an excess of the II genotype (5 vs. 9; chi 2 = 0.04, P = 0.83). Age, diabetes duration, age at diabetes onset, and HbA1c were not different according to genotype. Patients with glomerular hyperfiltration had low plasma ACE levels, compared with those with normal glomerular filtration (457 +/- 157 vs. 553 +/- 186 micrograms/l; P = 0.027). CONCLUSIONS: These results suggest an unexpected association between glomerular hyperfiltration and ACE (I/D) polymorphism, characterized by a defect of the DD genotype among type 1 diabetic children and adolescents with glomerular hyperfiltration.     

Long-term renoprotective effects of losartan in diabetic nephropathy: interaction with ACE insertion/deletion genotype?

OBJECTIVE: Several observational follow-up studies have found that the D allele of the insertion (I)/deletion (D) polymorphism of the ACE gene (ACE/ID) is associated with an increased risk of renal function loss, even during ACE inhibition. Therefore, we investigated the long-term effect of the angiotensin II subtype-1 (AT1) receptor antagonist losartan (100 mg o.d.) on kidney function in II and DD type 1 diabetic patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS: A total of 54 hypertensive type 1 diabetic patients with diabetic nephropathy homozygous for the insertion (n = 26) or the deletion (n = 28) allele were included in the study. After a 4-week washout, the patients received losartan (tablet, 100 mg o.d.) and were followed prospectively with a mean follow-up period of 36 months. Patients and investigators were blinded to ACE genotypes. At baseline, after 2 and 4 months and every 6 months thereafter, glomerular filtration rate (GFR), albuminuria, and 24-h blood pressure were determined. RESULTS: At baseline, GFR, albuminuria, and blood pressure were similar in the two genotype groups, II versus DD: mean (SD), 86 (22) vs. 88 (24) ml. min(-1). 1.73 m(-2); median (interquartile range), 1,134 (598-2,023) vs. 1,451 (893-1,766) mg/24 h; and mean (SD), 156/82 (17/9) vs. 153/80 (17/11) mmHg, respectively. GFR decreased similarly in both genotype groups, versus DD, respectively (P = 0.4): geometric mean (95% CI), 2.9 (2.0-4.2) vs. 3.4 (2.3-5.1) ml. min(-1). year(-1). Albuminuria and arterial blood pressure were significantly reduced during the study; no differences were noted between groups. During follow-up, albuminuria was decreased by 75% (95% CI 59-85) and 73% (56-83) in the II and DD groups, respectively (P < 0.01 vs. baseline). Mean systolic and diastolic blood pressures were 139/74 mmHg (14/8) in both genotype groups during the study (P < 0.01 vs. baseline). CONCLUSIONS: In contrast to previous observational studies with ACE inhibitors, long-term treatment with losartan has similar beneficial renoprotective effects on progression of diabetic nephropathy in hypertensive type 1 diabetic patients with ACE II and DD genotypes.     

ACE gene polymorphism as a prognostic indicator in patients with type 2 diabetes and established renal disease.

OBJECTIVE: To investigate whether the DD genotype is a predictor of mortality and of the decline in renal function in patients with type 2 diabetes and established nephropathy. RESEARCH DESIGN AND METHODS: A total of 56 such patients of Maltese Caucasian descent were recruited, and their ACE genotype was determined. Serum creatinine was estimated approximately every 4 months. The glomerular filtration rate (GFR) was calculated according to the Cockroft-Gault formula, and rate of change was determined by regression analysis. RESULTS: The rate of change in calculated GFR was -7.76 ml.min(-1).year(-1) in those with the DD genotype (n = 31) and -1.17 ml. min(-1). h(-1) in those with the ID or II genotype (n = 25) (P < 0.01). The 3-year mortality was 45.2% in the DD group compared with 20.0% in the ID/II group (P < 0.05). CONCLUSIONS: The DD genotype of the ACE gene polymorphism is associated with a more rapid decline in renal function and higher mortality in type 2 diabetic patients with established nephropathy.     

Interaction between angiotensin-converting enzyme genotype and glycaemic control influences lipoprotein levels in type 2 diabetes mellitus

AIMS: To evaluate the influence of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism on lipid levels in patients with Type 2 diabetes. PATIENTS AND METHODS: 109 patients with Type 2 diabetes were included. The patients were not on any lipid-lowering treatment. The groups with different ACE genotypes had similar ages, sex distributions, body mass indices, systolic blood pressures and indices of glycaemic control. ACE gene I/D polymorphism was determined using polymerase chain reaction. RESULTS: The mean apolipoprotein B (apoB) level was significantly higher in the group of DD homozygotes compared with the subjects with at least one insertion allele (DD: 1.21 +/- 0.25 g/l vs. ID + II: 1.04 +/- 0.27 g/l; P = 0.007). Significant correlations between glycated haemoglobin (HbA1c) and both apoB and cholesterol levels were found (r = 0.27; P < 0.01). For the apoB, this correlation was highly significant in the DD-genotype subgroup (r = 0.54; P < 0.01), and was not significant in the subgroup of patients with genotypes ID or II. In the multivariate analysis, HbA1c and the interaction of genotype DD with HbA1c were significant independent predictors of apoB (r2 = 0.17) and cholesterol levels. CONCLUSION: The present study showed that the interaction between the DD genotype of angiotensin-converting enzyme and chronic hyperglycaemia (expressed by HbA1c level) is related to higher plasma levels of atherogenic lipoproteins, such as apoB and cholesterol, in patients with Type 2 diabetes.     

血管紧张素转换酶基因多态性与2型糖尿病视网膜病变的相关性研究

目的探讨血管紧张素转换酶(ACE)基因多态性与2型糖尿病患者合并视网膜病变的关系。方法采用聚合酶链反应技术检测146例2型糖尿病患者ACE基因内含子16插入/缺失多态性,其中合并视网膜病变组27例,未发生视网膜病变组119例;同时选择200例健康志愿者作为正常对照组。结果合并视网膜病变组的ACE基因DD纯合型频率比未患视网膜病变组显著升高(70%与46%,P=0.042),但两组D等位基因频率比较无显著差异(80%与69%,P>0.05)。多因素分析表明,ACE基因DD基因型多态性与收缩压均为2型糖尿病视网膜病变的独立危险因素。结论ACE基因的DD基因型可增加2型糖尿病患者并发视网膜病变的危险性。     

血管紧张素转化酶基因I/D多态性与维吾尔族高血压合并阻塞性睡眠呼吸暂停低通气综合征患者左心室肥厚的关系

目的探讨血管紧张素转化酶(ACE)基因插入/缺失(I/D)多态性与维吾尔族高血压合并阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者左心室肥厚(LVH)的关系。 方法选取2015年1月至2016年12月于新疆医科大学第一附属医院高血压科首诊住院,且未服用血管紧张素转换酶抑制剂/血管紧张素Ⅱ受体拮抗剂(ACEI/ARB)类降压药物的维吾尔族高血压合并OSAHS患者,共72例,行多导睡眠呼吸监测、动态血压、心脏彩超等检查,聚合酶链式反应(PCR)和琼脂糖凝胶电泳技术测定ACE基因多态性。根据左心室质量指数分为左心室肥厚组(LVH组,n＝24)和非左心室肥厚组(NLVH组,n＝48),比较两组间基因型及基因频率的差异,使用多因素Logistic回归分析左心室肥厚的影响因素。 结果高血压合并OSAHS患者LVH组ACE基因型频率分别为：II(37.50%),ID(20.83%),DD(41.67%),等位基因频率分别为：I(48.00%),D(52.00%),与NLVH组[II(47.92%),ID(37.50%),DD(14.58%),I(67.00%),D(33.00%)]比较,差异有统计学意义(χ²＝6.75,4.70;均P<0.05);对左心室肥厚影响因素进行多因素Logistic回归分析,呼吸暂停低通气指数(AHI)(OR＝6.20,95%CI：1.44～26.77;P<0.05)、DD基因型(OR＝4.61,95%CI：1.05～20.31;P<0.05)是维吾尔族高血压合并OSAHS患者发生LVH的独立危险因素。 结论ACE基因I/D多态性与维吾尔族高血压合并OSAHS患者发生LVH有关,其中DD基因型维吾尔族患者更易发生LVH。     

Influence of oxygen administration on pulmonary haemodynamics and tissue oxygenation during exercise in COPD patients with different ACE genotypes

We previously found that the angiotensin-converting enzyme (ACE) DD genotype is associated with exaggerated pulmonary hypertension and disturbance of tissue oxygenation during exercise in chronic obstructive pulmonary disease (COPD) patients. This study was designed to compare the effect of oxygen administration on pulmonary haemodynamics and tissue oxygenation during exercise in COPD patients with different ACE genotypes. Forty-three COPD patients (II=16, ID=12, DD=15) underwent right heart catheterization, and then performed an exercise test with room air or oxygen. We measured pulmonary haemodynamic variables and indices of tissue oxygenation such as mixed venous oxygen tension (PVO2) and arterial lactate concentration, both at rest and after exercise. The magnitude of difference in mean pulmonary arterial pressure and pulmonary vascular resistance after exercise between breathing of room air and breathing of oxygen did not significantly differ among the three groups. PVO2 after exercise with room air or oxygen was significantly higher in patients with the II genotype than in those with the ID or DD genotype. In contrast, lactate concentration after exercise with room air or oxygen was significantly lower in patients with the II genotype than in those with the ID or DD genotype. Moreover, the magnitude of difference in PVO2 and lactate concentration after exercise between breathing of room air and breathing of oxygen was the II>ID>DD genotype. These findings suggest that the ability of oxygen administration to improve tissue oxygenation during exercise is associated with the ACE genotypes in COPD patients.     

Cardiovascular morbidity and early mortality cluster in parents of type 1 diabetic patients with diabetic nephropathy

OBJECTIVE: A familial predisposition was proposed to be a determinant of the increased morbidity and mortality from cardiovascular disease in type 1 diabetic patients with diabetic nephropathy. The insertion allele of an insertion/deletion polymorphism in the ACE (ACE/ID) gene seems to protect against coronary heart disease in nondiabetic and diabetic subjects. The aim of the present study was to evaluate these hypotheses in parents of a large group of type 1 diabetic patients with and without diabetic nephropathy. RESEARCH DESIGN AND METHODS: We investigated cardiovascular morbidity and mortality of parents of 163 type 1 diabetic patients with nephropathy and parents of 163 sex- and age-matched normoalbuminuric patients with type 1 diabetes. RESULTS: Kaplan-Meier curves showed that total parental mortality was significantly increased in parents of type 1 diabetic patients with nephropathy (121 of 244 [ approximately 50%] ) as compared with parents of normoalbuminuric type 1 diabetic patients (119 of 269 [approximately 44%]) (P = 0.008 [log-rank test]) partially due to an increase in cardiovascular deaths (48 of 244 [approximately 20%] vs. 42 of 269 [approximately 16%], P<0.05). In addition, more patients with nephropathy, as compared with the normoalbuminuric group, had at least one parent with fatal/nonfatal cardiovascular disease (46% [95% CI 38-54] vs. 36% [28-44], P = 0.05). Fathers of patients homozygous for the I-allele of the ACE/ID polymorphism had significantly less myocardial infarction as compared with other genotypes (P = 0.03), regardless of the nephropathic state of the offspring. CONCLUSIONS: Cardiovascular morbidity and early mortality clusters in parents of type 1 diabetic patients with diabetic nephropathy The ACE/ID polymorphism helps explain the increased morbidity from cardiovascular disease.     

小剂量氢氯噻嗪降压疗效影响因素分析

目的 探讨影响小剂量氢氯噻嗪（HCTZ）降压疗效的因素。方法 829例高血压患者服用HCTZ12．5mg，1次／d，共6周。以资料完整的805例患者为对象分析影响HCTZ降压疗效的因素。结果 Ⅱ、ID、DD基因型患者收缩压下降值分别为5．4、4．4和12．2mmHg，DD基因型患者收缩压下降值大于Ⅱ及ID两型患者，差异有统计学意义（P〈0．05）。Ⅱ、ID、DD基因型患者平均动脉压下降值分别为3．9、3．6和6．9millHg，3组差异有统计学意义（P〈0．05）；3组患者舒张压下降值差异无统计学意义（P〉0．05）；DD型患者总有效率最高；DD型患者的显效率、有效率高于Ⅱ、ID两型患者（P〈0．05）；多元线性回归结果表明治疗前收缩压水平、DD基因型、治疗前醛固酮浓度影响收缩压下降水平；治疗前舒张压水平、治疗前醛固酮浓度、DD基因型影响舒张压下降值；治疗前平均动脉压水平、DD基因型、治疗前醛固酮浓度影响平均动脉压下降值。结论 不同ACE基因型患者对HCTZ的疗效存在差异，DD基因型患者降压疗效好于Ⅱ、ID两型患者；治疗前血压水平、醛固酮浓度与HCTZ的降压疗效有关。