子痫前期肾素血管紧张素系统基因多态性及其相互作用的相关性研究

目的 探讨血管紧张素转换酶（ACE）基因插入／缺失（I/D），血管紧张素原（AGT）基因M235T，血管紧张素Ⅱ1型受体（AT1R）基因A1166C位点多态性与子痫前期发病的关系。方法 采用聚合酶链反应（PCR）和聚合酶链反应-限制性片段长度多态性（PCR—RFLP）方法检测58例子痫前期孕妇，102例正常妊娠孕妇的ACEI／D，ACTM235T，AT1RA1166C位点多态性。结果 子痫前期组ACEDD型占48．3％（P〈0．05，优势比[OR]2．04），Ⅱ型占8．6％（OR0．34），子痫前期组与对照组相比D等位基因频率显著增加（P〈0．01，OR1．9）。AGTM235T，AT1RA1166C多态性与子痫前期无明显相关。子痫前期三个基因的基因型之间无明显协同作用。结论 ACEDD型可能增加妊娠期高血压疾病患病风险，ACEI／D，AGTM235T，AT1RA1166C多态性在子痫前期发病危险性上无明显协同作用。     

性别差异对服用氢氯噻嗪后不同ACE基因型高血压患者血清RAAS活性变化的影响

目的:探讨性别差异对不同血管紧张素转换酶(ACE)基因型高血压患者服用氢氯噻嗪后血清肾素-血管紧张素-醛固酮系统(RAAS)活性变化的影响。方法:根据自愿原则,随机纳入829例轻、中度高血压患者。所有患者均停服原有的抗高血压药物,并经过2周的安慰剂清洗期,随后口服氢氯噻嗪12.5mg,qd,连续服药6周。分析不同性别、ACE基因型患者服用氢氯噻嗪后血清RAAS水平的变化及二者之间的交互作用。结果:共776例研究对象完成了研究并纳入分析。DD基因型男性患者服用氢氯噻嗪6周后血清ACE和血管紧张素Ⅱ(AngⅡ)水平升高幅度均高于II、ID基因型男性患者(P<0.05);而在女性中,DD基因型患者血清ACE和AngⅡ水平升高幅度却明显低于II、ID基因型女性患者(P<0.05)。性别与ACE基因插入/缺失(I/D)多态性对服用氢氯噻嗪后血清ACE水平变化存在明显交互作用(P=0.032),对血清AngⅡ水平变化存在临界交互作用(P=0.070)。结论:校正年龄、体重指数和基线血压水平后,性别与ACE基因I/D多态性对服用氢氯噻嗪后血清ACE水平变化存在明显交互作用。     

血管紧张素转化酶基因多态性与血管紧张素转化酶和血管紧张素Ⅱ水平的关系

目的探讨原发性高血压患者血管紧张素转化酶(ACE)基因插入/缺失(I/D)多态性与血清ACE和血管紧张素Ⅱ浓度的关系。方法应用PCR技术测定518例高血压患者的ACE基因型,并测定其ACE、血管紧张素Ⅱ浓度。结果II、ID、DD型患者血浆ACE浓度分别为(33.84±15.99)U/L、(41.1±16.80)U/L、(50.34±18.92)U/L,三种基因型之间的差异有统计学意义(P<0.05);血浆血管紧张素Ⅱ浓度在三种基因型之间的差异无统计学意义(P>0.05)。结论ACE基因多态性与血浆ACE浓度相关,而与血浆血管紧张素Ⅱ浓度无关。     

细胞色素P450 2C9和血管紧张素Ⅱ1型受体基因多态性与血管紧张素Ⅱ受体拮抗剂厄贝沙坦降压疗效的关系

目的 观察血管紧张素Ⅱ1型受体(AT1R)和细胞色素 P450 2C9(CYP2C9)基因变异对高血压患者血管紧张素Ⅱ1 型受体拮抗剂降压疗效个体差异的影响.方法 入选高血压患者 76 例,予单药厄贝沙坦每天 150 mg,治疗 8 周,观察降压疗效.提取血中 DNA,分别用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)和微阵列技术进行单核苷酸多态性(SNP)位点(AT1R 1166A/C、573 T/C、-521 C/T,CYP 2C9 1075A/C、1080C/G)的基因型分析.结果 含 AT1R 573 T 等位基因患者,服用厄贝沙坦后,收缩压下降幅度明显大于 CC 基因型患者,分别为(16.47±11.75) vs (7.44±7.50)mm Hg(P＜0.05)而 AT1R 1166A/C、-521 C/T、CYP 2C9 1075A/C、1080C/G 各基因型服药后,血压下降幅度均无显著差异.结论 厄贝沙坦作用受体 AT1R 基因 SNP 位点 573 T/C 可能与其降压疗效有关;未发现 CYP 2C9 基因上的两个 SNP 位点与厄贝沙坦的降压疗效有关.     

伊贝沙坦对不同ACE基因多态性肾病病人疗效对比

目的 探讨血管紧张素Ⅱ（AngⅡ）受体拮抗剂对不同血管紧张素转换酶（ACE）基因肾病患者疗效有无差异。方法：分别检测糖尿病肾病8例，高血压肾病9例，慢性肾功能衰竭12例病人的ACE基因I／D多态性。实验前2个月病人禁用血管紧张素转化酶抑制剂（ACEI）。原治疗方案不变，在服药前查24h尿蛋白定量、血肌酐（Cr)、尿素氮（BUN）。之后给予血管紧张素Ⅱ受体拮抗剂－伊贝沙坦150mg，每日一次口服，共8周，结束后复查上述三个项目。结果：三种基因型肾病患者治疗前各项指标比较无显著性差别（P＜0．05），治疗后尿蛋白明显减少。血肌酐及尿素氮治疗前后则无明显差别。29例病人均未出现明显不适。结论 AngⅡ受体拮抗剂治疗肾脏疾病降低尿蛋白的作用与ACE基因I／D多态性无关，即伊贝沙坦对三种ACE基因型肾病病人降尿蛋白均有显著作用且耐受性良好。     

血管紧张素转化酶基因多态性与Ⅱ型糖尿病肾病

目的探讨血管紧张素转化酶(ACE)基因插入/缺失多态性与Ⅱ型糖尿病(NIDDM)肾病的关系。方法聚合酶链反应。结果无肾病的NIDDM患者中 ,ACE基因型频率与正常人比较 ,I/I基因型和I/D D/D基因型频率分布差异有显著性意义(P<0.05) ;有肾病的NIDDM患者中 ,ACE基因型频率与正常人比较 ,D/D基因型和I/D I/I基因型频率分布差异有显著性意义(P<0.05)。结论I/I基因型是NIDDM肾病患者的保护性基因 ;而D/D基因型是NIDDM肾病患者的易感基因     

ACE基因多态性与ACE、血管紧张素Ⅱ及醛固酮的关系

目的:探讨原发性高血压患者血管紧张素转化酶(ACE)基因插入/缺失(I/d)多态性与血清ACE、血管紧张素Ⅱ及醛固酮的关系。方法:应用PCR技术测定146例高血压患者的ACE基因型,并测定其血清ACE、血管紧张素Ⅱ及醛固酮浓度。结果:ACE在DD、ID、Ⅱ三种ACE基因型之间的差异有显著性,ACE活性DD>IDⅡ,而血管紧张素Ⅱ及醛固酮在三种基因型之间的差异无显著性。结论:ACE基因多态性与ACE密切相关,而与血清血管紧张素Ⅱ及醛固酮没有关系。     

血管紧张素转换酶基因多态性与血管紧张素转换酶抑制剂的降压作用

目的:从基因多态性研究药效的差异。方法:选择健康志愿者99 例,未治疗的原发性高血压病人40 例,用PCR 方法检测血管紧张素转换酶(ACE) 基因的插入与缺失(I/D) 多态性, 用血管紧张素转换酶抑制剂(ACEI) 卡托普利治疗高血压病人。结果:正常人与原发性高血压患者的ACE等位基因频率及基因型频率无显著差异(P>0.05) 。卡托普利降压有效病人与无效病人ACE 基因的I/D等位基因频率及基因型频率,基因缺失型纯合子(DD)或/ 和杂合子(ID) 与非缺失型(II) 也均无显著差异(P>0.05) 。结论: ACE基因的I/ D多态性与原发性高血压的发病无关, ACEI降压作用的个体差异与ACE基因的I/D多态性无关。     

ACE基因多态性与冠心病的相关性研究

目的测定中国汉族人群血管紧张素转换酶基因插入/缺失(I/D)多态性,研究其在中国汉族人群中的分布以及与冠心病发生的关系。方法冠心病患者146例,均经冠状动脉造影确诊;正常对照组113例,选自人群健康查体的随机个体。应用聚合酶链反应-限制性片断长度多态性分析,聚丙稀酰胺凝胶电泳方法检测ACE基因插入/缺失(I/D)多态性。结果①中国汉族人群血管紧张素转换酶基因有Ⅱ、ID、DD三种基因型;②ACE基因I/D多态性与冠心病相关,具有DD基因型比具有Ⅱ基因型的人患冠心病的危险性增加2.06倍。结论①中国汉族人群血管紧张素转换酶基因有Ⅱ、ID、DD三种基因型;②血管紧张素转换酶基因插入/缺失(I/D)多态性与冠心病相关。     

ACE基因多态性与原发性高血压患者血清ACE和血浆AngⅡ水平的相关性

目的研究血管紧张素转化酶(ACE)基因插入/缺失(I/D)多态性与原发性高血压(EH)患者血清ACE、血浆血管紧张素Ⅱ(AngⅡ)水平的相关性。方法选择青岛地区EH患者246例和130例正常对照,测定两组血压、血脂、血糖等临床及生化指标,并对高血压进行分级,同时检测血清ACE、血浆AngⅡ水平,采用聚合酶链反应(PCR),检测ACE基因型,比较不同基因型、不同血压分级患者其血清ACE、血浆AngⅡ水平有无差别。结果EH组中,II、ID、DD基因型患者血清ACE水平分别为(36.69±14.05)U/L,(42.98±16.61)U/L,(49.37±17.43)U/L,组间差异有统计学差异(P<0.05);三组基因型患者血浆AngⅡ水平比较,组间差异无统计学差异(P>0.05);随着高血压分级的升高,血清ACE及血浆AngⅡ水平逐渐增加,差异均有统计学意义(P<0.05);EH患者血清ACE水平与ACE基因多态性之间有相关性(r=0.324,P<0.05)。结论 DD基因型EH患者血清ACE水平明显高于ID型和II型患者,血浆AngⅡ水平在不同基因型间无统计学差异。     

Impact of renin-angiotensin-aldosterone system genes on the treatment response of patients with hypertension and metabolic syndrome.

OBJECTIVE: To evaluate the influence of clinical, biochemical and genetic markers on the response to antihypertensive treatment in patients with essential hypertension and the metabolic syndrome (MetS). METHODS: Measurements of anthropometric indices, blood pressure (BP), and metabolic parameters were obtained from the medical records of 132 (77 women) newly diagnosed, untreated hypertensive patients. Renin-angiotensin-aldosterone system (RAAS) genes polymorphisms (including ACE I/D, angiotensinogen M235T, angiotensin II type 1 receptor [AT1-receptor] A1166C) were determined. Response to treatment was defined as BP less than 140/90 mmHg. RESULTS: Patients with MetS (n=60) had higher systolic BP and pulse pressure and a more atherogenic lipid profile than patients without MetS. The frequencies of the ACE and the AT1-receptor gene polymorphisms were similar between patients with and without MetS. Response to treatment was positively associated with pulse pressure, and the presence of the C allele as well as the AC genotype of the AT1-receptor gene and inversely with age after adjustment for confounding factors. CONCLUSIONS: RAAS genes distribution does not differ between hypertensive patients with and without the MetS. Higher baseline pulse pressure levels, the presence of the C allele and/or the AC genotype may be in favour of a better response to structured antihypertensive treatment in patients with MetS. However, these findings need to be evaluated in future studies.     

Association of Angiotensinogen (M235T) Gene Polymorphism with Blood Pressure Lowering Response to Angiotensin Converting Enzyme Inhibitor (Enalapril)

Purpose: It has been suggested that genetic backgrounds, which have an association with essential hypertension, may also determine the responsiveness to ACE inhibitor. We determined the association of angiotensinogen (M235T) gene polymorphism with essential hypertension and the relationship between polymorphism in the angiotensinogen (M235T) gene and blood pressure response to ACE inhibitor (Enalapril) in patients with essential hypertension from northern Indian subjects. Methods: 250 patients with essential hypertension and 250 normal healthy controls from Delhi and surrounding areas were recruited for the investigation. Blood pressure was recorded before and after 6 weeks of treatment with ACE inhibitors, Enalapril. Genotyping were carried out by polymerase chain reaction and Restriction fragment length polymorphism technique. Results: Statistically significant association of T allele was observed with essential hypertension [x2 = 14.67, p = 0.00013, Odds ratio = 1.76 (1.3-2.32) at 95% CI], the relative risk at 95% CI being 1.28 (1.2-1.54). The decrease in systolic blood pressure and diastolic blood pressure after six weeks of treatment of the patients carrying TT genotype (SBP = 26±17.4 mmHg, DBP = 14.83±7.6mmHg) were greater than the groups carrying MT (SBP = 3.0±7.8 mmHg, DBP =6.2±3.0 mmHg) and MM genotypes (SBP = 1.2±0.8 mmHg, DBP = 0.10±12.1 mm Hg. Conclusions: The angiotensinogen (M235T) gene polymorphism is significantly associated with essential hypertension. Patients carrying TT genotype had higher blood pressure lowering response when treated with ACE inhibitor, Enalapril than those carrying MM and MT genotypes suggesting that the T allele may be a possible genetic marker for essential hypertension. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.     

Interaction of A-240T and A2350G related genotypes of angiotensin-converting enzyme (ACE) is associated with decreased serum ACE activity and blood pressure in a healthy Iranian population

Most of renin-angiotensin system (RAS) gene polymorphisms have not yet been studied in the Iranian population. In the present study, the frequencies of common polymorphisms in the RAS genes, including angiotensin-converting enzyme (ACE) insertion/deletion (I/D) and three single-nucleotide polymorphisms (SNPs), i.e., A-240T, T-93C and A2350G, angiotensinogen M235T, angiotensin II receptor type 1 A1166C and angiotensin II receptor type 2 C3123A variants were determined in DNAs extracted from venous blood of 104 healthy Iranian volunteers. Genotyping was performed by PCR-RFLP method. Serum ACE activity was also assayed using reverse phase HPLC. Combined polymorphisms of TT (A-240T) and GG (A2350G) was significantly associated with decreased serum ACE activity (P=0.042) and decreased diastolic blood pressure (P=0.040). The angiotensin II receptor type 1 A1166C polymorphism (CC genotype) showed a significant association with declined diastolic blood pressure (P=0.028). Serum ACE activity was significantly higher in men compared to women (P=0.033). ACE activity also showed a direct association with diastolic blood pressure (P<0.001). No association was obtained among each single polymorphism with body mass index (BMI), fasting blood sugar (FBS), lipid profile and ACE activity. In conclusion, combined polymorphisms of A-240T and A2350G seem to affect serum ACE level as well as diastolic blood pressure in our study population. However, it also might be hypothesized that they are in strong linkage disequilibrium with other functional mutations not studied yet. Our findings revealed that gene interactions can play an important role in various biological conditions.     

Genetic polymorphisms of the renin-angiotensin system in preterm delivery and premature rupture of membranes.

INTRODUCTION: Premature rupture of membranes (PRM) is a late pregnancy complication commonly associated with preterm delivery (PD). Although several markers related to the renin-angiotensin system (RAS) have been evaluated in certain pregnancy complications, only the angiotensin-converting enzyme (ACE) I/D variant has been studied in PD-PRM. The aim of this survey was to investigate the association of the polymorphisms (angiotensin II type 1 [AT1] receptor T174M and M235T, renin G2805A, ACE I/D and AT1-receptor A1166C) of the genes of RAS in women with PD-PRM. DESIGN: Deoxyribonucleic acid samples from 89 Mexican Mestizo women with PD and PRM and 224-288 controls were studied. Polymorphisms were analysed by polymerase chain reaction-restricted fragment length polymorphism or sequence specific primer assays. RESULTS: For all loci, genotype distribution was in agreement with Hardy-Weinberg expectations in the control group. Significant intergroup difference (case vs. control) was seen for angiotensinogen (AGT) M235T polymorphism, with an increased allele M235 in affected cases (50% vs. 40% in controls). Analysis of two-locus haplotype agrees with an independent segregation of physically unlinked genes. Haplotype AGT 174T-235M was also increased (50% vs. 40% in controls). CONCLUSIONS: Physically unlinked genes involved in RAS segregate independently. The AGT 174-235 region is associated with PD-PRM in this population.     

Renal haemodynamics are not related to genotypes in offspring of parents with essential hypertension.

INTRODUCTION. The pathogenesis of essential hypertension (EH) has a major genetic component and is associated with renal abnormalities. Normotensive offspring of hypertensive parents are likely to develop EH and are a suitable population for identifying possible relations between genetic and renal abnormalities. METHODS: We investigated if renin-angiotensinaldosterone system associated genotypes (angiotensinogen [M235T] and ACE [I/D]) are related to blood pressure (BP), renal haemodynamics and sodium excretion in sex and age-matched (1835 years) healthy Caucasian offspring of either two parents with EH (n=101, EH-offspring) or two normotensive parents (n=50, controls). The alpha-adducin polymorphism (G460W) was also investigated. RESULTS: Compared to controls, BP, heart rate, renal vascular resistance (RVR) and urinary sodium excretion were, respectively, 5%, 7%, 15% and 20% higher in EHoffspring. In controls, the TT-genotype of the M235T angiotensinogen polymorphism was associated with higher BP and higher plasma angiotensinogen. By contrast, in EHoffspring the TT-genotype was associated with lower BP and unchanged plasma angiotensinogen. Plasma angiotensinogen correlated positively with BP in EH-offspring, with a similar tendency (p=0.08) in controls. The distributions of the three candidate polymorphisms were similar in EH-offspring and controls. There were no associations between any of the polymorphisms and any of the renal parameters measured. CONCLUSION: The markedly greater RVR, proportionally larger than the greater BP, supports a role for RVR in the pathogenesis of EH. The lack of association between the candidate polymorphisms and the investigated parameters, even in this homogenous and for hypertension strongly predisposed group, suggests that the polymorphisms investigated do not play important roles in the pathogenesis of hypertension.     

Pharmacogenomic considerations of the insertion/deletion gene polymorphism of the angiotensin I-converting enzyme and coronary artery disease

Gene polymorphisms of components of the renin-angiotensin system, angiotensinogen, angiotensin I-converting enzyme (ACE) and angiotensin II type 1 receptor (AT-1), have been considered to contribute to inherited predisposition towards coronary artery disease (CAD). The best analyzed is the insertion/deletion (I/D) gene polymorphism of the ACE gene. Several studies suggest that the ACE D allele is associated with the occurrence of CAD and myocardial infarction. Moreover, the I/D polymorphism of the ACE gene has been thought to be related to diverse responses to drugs. Modern gene technologies may therefore provide the information, which may help to identify disease-associated genes and determine the responsiveness to a given drug.     

Effects of genetic polymorphisms of the renin-angiotensin system in children with nephrotic syndrome.

BACKGROUND: The renin-angiotensin system (RAS) has been considered to be responsible for the pathogenesis or progression of many diseases which may or may not be related to kidney. Genetic polymorphisms of the various components of the RAS have been associated with differences in the clinical course of several disease states in adults and children. OBJECTIVES: The purpose of our study was to investigate RAS gene polymorphisms in patients with steroid resistant primary focal segmental glomerulosclerosis (FSGS) and nephrotic syndrome responding to steroid therapy. Furthermore, we aimed to investigate whether there was an association between polymorphic alleles and responses to steroid therapy, the degree of renal dysfunction, and prevalence of end-stage renal disease (ESRD). MATERIAL AND METHODS: One hundred and fifty-eight children with the diagnosis of nephrotic syndrome were recruited from the Nephrology unit in the Department of Paediatrics of Ege University. Forty-nine of them were classified as renal biopsy-proven FSGS and 102 patients were considered to have response to steroid treatment. Renal functional impairment was detected in 19 subjects with FSGS and end-stage renal insufficiency in 13 patients. The control group consisted of 287 healthy adult subjects. Angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor (AT1R) and angiotensinogen (AGT) gene polymorphisms were determined by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique. Statistical significance was regarded as p<0.05. RESULTS: There were no statistically significant differences for the C allele of AT1R or the T allele of AGT genes between the children with nephrotic syndrome and control group, but on the other hand statistically significant differences were detected for D allele of ACE gene. There was no significant relationship detected between the D allele of ACE, the C allele of AT1R or the T allele of AGT genes and response to steroid therapy, extent of renal dysfunction and the progression to ESRD. However, there was a significant relationship between T allele of AGT gene and resistance to steroid treatment (OR; 4,837, 95% CI; 1,723-13,577, p=0.01), renal dysfunction (OR; 3,189, 95% CI; 0,999-10,182, p=0.041) and progression to ESRD (OR; 3,852, 95% CI; 1,057-14,040, p=0.03). CONCLUSION: In this study, the angiotensinogen -235T allele was found to be related with steroid resistance, renal dysfunction and progression of ESRD in nephrotic syndrome.     

Angiotensinogen and ACE gene polymorphisms and risk of atrial fibrillation in the general population

OBJECTIVES: The renin-angiotensin system may play a role in the pathogenesis of atrial fibrillation, and renin-angiotensin system blockers reduce the risk of atrial fibrillation. We hypothesized that polymorphisms in the angiotensinogen and angiotensin-converting enzyme (ACE) genes encoding proteins in this system predict risk of atrial fibrillation. METHODS AND RESULTS: We genotyped 9235 individuals from the Danish general population, The Copenhagen City Heart Study, for the a-20c, g-6a, T174M, and M235T polymorphisms in the angiotensinogen gene and the insertion/deletion (I/D) polymorphism in the ACE gene; rare allele frequencies were 0.16, 0.40, 0.12, 0.41, and 0.49, respectively. Participants had sinus rhythm at inclusion. During 26 years of follow-up, 968 individuals developed atrial fibrillation. Multifactorially adjusted hazard ratios for atrial fibrillation for a-20c ac and cc versus aa genotype were 1.1(95% confidence interval: 1.0-1.3; P=0.05) and 1.5(1.1-2.1; P=0.01). Compared with double noncarriers (angiotensinogen -20aa and ACE II), double heterozygotes (ac-I/D genotype), and double homozygotes (cc-DD) had hazard ratios for atrial fibrillation of 1.2(0.9-1.6; P=0.06) and 2.4(1.4-4.1; P=0.001). a-20c cc homozygotes above 70 years of age who were overweight, severely hypertensive, and had heart failure, had an absolute 10-year risk of atrial fibrillation of 61%. CONCLUSION: Angiotensinogen a-20c genotype alone and in combination with ACE I/D genotype predicts an increased risk of atrial fibrillation. Therefore, genetic variation in the renin-angiotensin system may influence effect of renin-angiotensin system blockers on atrial fibrillation.     

Pharmacogenetic interactions of three candidate gene polymorphisms with ACE-inhibitors or beta-blockers and the risk of atherosclerosis

AIMS: To investigate whether the angiotensin-converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen M235T or angiotensin II receptor type 1 573C/T polymorphism modify the risk of atherosclerosis associated with beta-blocker or ACE-inhibitor therapy. METHODS: Data were used from the Rotterdam Study, a population-based prospective cohort study in the Netherlands, which started in 1990 and included 7983 subjects of >or= 55 years. In this study, 2216 subjects with hypertension were included. Three subclinical measurements were used for atherosclerosis, i.e. peripheral arterial disease, carotid atherosclerosis and aortic atherosclerosis. The interaction between antihypertensive drugs and genetic polymorphisms on the risk of atherosclerosis was determined with binary logistic regression analysis. RESULTS: The risk of aortic atherosclerosis associated with long-term (>or=4 years) beta-blocker treatment compared with no use of beta-blockers was higher in subjects with the TT genotype than in subjects with the MM genotype of the AGT gene [synergy index (SI) = 3.36; 95% confidence interval (CI) 1.14, 9.97]. The risk of carotid atherosclerosis associated with long-term ACE-inhibitor treatment compared with no use of ACE-inhibitors was lower in subjects with the TT genotype than in subjects with the MM genotype of the AGT gene (SI = 0.20; 95% CI 0.04, 0.95). CONCLUSION: Overall, the risk of atherosclerosis in hypertensives taking a beta-blocker or ACE-inhibitor-based regimen was not strongly modified by any of the three candidate gene polymorphisms.