中国人内源性高甘油三酯血症载脂蛋白E基因多态性的研究

目的 探讨中国人内源性高城油三酯血症（endogenous hypertriglyceridemia,HTG)患者载脂蛋白E（apolipoprotein E,apoE)基因多态性及其与血脂和载脂蛋白水平的关系。方法 采用聚合酶链反应－限制性片段长度多态性分析方法,分别对225例HTG患者及230名血脂正常者的apoE基因型、空腹血脂及载脂蛋白AⅠ、AⅡ、B100、CⅡ、CⅢ、E进行了分析。结果 HTG患者的体重指数(BMI)` 清甘油三酯（TG）、总胆固醇（TC）、非高密度脂蛋白胆固醇（nHDLC)水平较对照组显著升高,血清高密度脂蛋白胆固醇（HDLC）则显著降低（P＜0．001）,并伴有载脂蛋白水平的异常。HTG组与对照组apoE基因型及等位基因频率分布均以E3／3和ε3最高,HTG组的ε2等位基因有增高的趋势（P＞0．05）。对照组ε2等位基因携带者血清TG和apoE水平较ε3和ε4等位基因携带者显著升高（P＜0．001）,其低密度脂蛋白胆固醇（LDLC）水平及apoE/ApoC Ⅲ比值则显著降低（P＜0．001）。结论 ε2等位基因与血清TG和apoE水平升高及LDLC水平降低有关,apoE/apoC Ⅲ比值降低可能与HTG患者血TG水平升高有关。     

冠心病家族史青少年载脂蛋白E、B的基因多态性

目的 探讨青少年载脂蛋白E(apolipoprotein E，apoE)、apoB基因多态性对冠心病的遗传易感性。方法 应用聚合酶链反应—限制性片段长度多态性技术，对244名健康汉族大学生(冠心病家族史阳性者109人，阴性者135人)的apoE、apoB XbaI、apoB 3’可变数目串联重复序列(variable number of tandem repeat ，VNTR)基因型进行分析。结果 阳性组的e4、x^ 、VNTR—B(hypervariable element，HVE＞38)等位基因频率显著高于阴性组(P＜0．05)，且与血总胆固醇、低密度脂蛋白—胆固醇、aPoBl00水平升高有显著相关(P＜0．05)。结论 apoE的e4、apoB Xba I的x^ 、apoB3’VNTR的VNTR—B可能为冠心病的重要遗传标记。     

载脂蛋白E基因多态性与早发冠心病的关系及其对血脂的影响

目的 研究载脂蛋白E（apolipoprotein E,apoE)基因多态性与早发冠心病（coronary heart disease,CHD)的相关关系及其对血脂水平的影响。方法 应用聚合酶链反应－限制性片段长度多态性（polymerase chain reaction-restricted fragment hength polymorphism,PCR-RFLP)基因分析方法,测定52例早发CHD、161例迟发CHD患者和180名对照者的apoE基因型;血脂水平按常规方法测定。结果 发现的5种apoE基因型,分别为E3／3、E4／4、E3／2、E4／3及E4／2。早发CHD组和迟发CHD组apoE4/3基因型和ε4等位基因频率均高于对照组（P＜0．01）;进一步对两组CHD患者的apoE多态性进行分析,发现早发组ε4等位基因频率较迟发组为高（P＜0．05）。apoE各等位基因型之间,TC和LDL－C水平之间存在统计学差异（P＜0．05）。结论 apoE基因多态性与早发CHD的发生发展有关并影响血脂的水平。     

ApoE基因多态性对毛南族人群血清apoA1、apoB水平的影响

目的 探讨载脂蛋白（apo）E基因多态性对毛南族人群血清apoA1、apoB水平的影响。 方法 收集221名贵州省黔南州毛南族人群血样品,采用免疫透射比浊法测定血清apoA1、apoB浓度;应用聚合酶链反应-限制性片段长度多态性方法（PCR-RFLP）检测apoE2、E3、E4基因多态性。 结果 与apoE2/2+E2/3+E2/4基因型亚组（ n =37）比较,apoE3/4+E4/4基因型亚组（ n =41）和apoE3/3基因型亚组（ n =143）血清apoB水平升高（ P ＜0.05）,apoA1/B比值降低（P ＜0.05）;apoE3/4+E4/4基因型亚组apoB水平高于apoE3/3亚组（ P ＜0.05）。未发现不同apoE基因型亚组间血清apoA1水平差异存在统计学意义（ P ＞0.05）。结论 毛南族人群apoE基因多态性明显影响血清apoB水平和apoA1/B比值,但未见该基因多态性与血清apoA1水平相关联。     

冠心病患者apoE基因调控序列-219(G/T)多态性及与血脂的关系

为了研究载脂蛋白E(apoE）基因调控序列－219（G／T）多态性与人类冠心病（CHD）及其血脂水平的关系，本文采用聚合酶链反应结合了限制性片段长度多态性方法。分析了108例健康人及86例冠心病患者的－219（G／T）基因型。PCR产物直接测序验下。我们发现冠心病组apoE－219（T／T）基因型频率（0．651）和T等位基因频率（0．767）分别显著高于对照组（0．444，0．653，P＜0．05）；冠心病组和对照组T／T基因型者血清总胆固醇高于G／G基因型者。这一结果提示apoE调控区基因多态性可能影响冠心病的发生。推测apoE－219（T／T）基因型是冠心病的危险因子之一。     

脂蛋白脂酶Ser447Ter基因多态性与动脉硬化性脑梗死的相关研究

目的研究脂蛋白脂酶（lipoprotein lipase，LPL）Ser447Ter基因多态性与动脉粥样硬化性脑梗死（atherosclerotic cerebral infarction, CI）发病的关系及其对血脂水平、颈动脉斑块的影响。方法对166例CI患者及72名健康成人采用聚合酶链反应-限制性片段长度多态性方法检测LPL-Ser447Ter基因多态性，颈动脉超声多普勒检查颈总动脉内膜中层厚度（intima-media thickness，IMT）和颈动脉斑块（carotid artery plaque，CAP）的形状及大小。结果CI组CG＋GG基因型甘油三酯（triglyceride，TG）含量比CC基因型明显降低（P=0．1301），高密度脂蛋白胆固醇（high density lipoprotein cholesterol，HDL-C）含量明显增高（P=0．007）；对照组CG＋GG基因型TG含量比CC基因型低（P=0．041）；CI组G等位基因频率低于对照组（P=0．014）；LPLSer447Ter基因多态性与颈总动脉IMT和CAP分级无明显相关。结论LPL Ser447Ter基因多态性与血脂变化及脑梗死的关系密切，G等位基因可能引起血TG降低、HDL-C升高；G等位基因可能是脑梗死的保护基因型．     

中国人内源性高甘油三酯血症与脂蛋白脂酶基因PvuⅡ多态性关联的研究

目的：探讨中国人内源性高甘油三酯血症（hypertriglyceridemics,HTG)与脂蛋白脂酶基因PvuⅡ多态性是否关联。方法：采用聚合酶链反应和限制性片段长度多态性方法,对成都地区135例内源性高甘油三酯血症患者和193名血脂正常者脂蛋白脂酶基因内含子6PvuⅡ多态性及其对血脂及载脂蛋白（apo)水平的影响进行了研究。结果：HTG患者和正常人均以P＋等位基因为主,HTG组以P＋P＋基因型为主,而正常对照组P＋P－基因型为主。HTG组的P＋P＋基因型分布频率及P＋等位基因分布频率则显著高于正常对照组（0.460vs0.337,P＜0.05;0.689vs0.565,P＜0.01)。P＋P＋基因型者的血清甘油三酯（TG）、apoCⅡ、apoCⅢ、apoE水平及TG／HDL－C比值较P－P－基因型者显著增高（P＜0．05）。结论：脂蛋白酯酶基因P＋P＋基因型与中国人内源性高甘油三酯血症的遗传易感性有一定关联。     

阿尔茨海默病与载脂蛋白E基因-427C/T多态性的关联研究

目的 探讨上海地区汉族人群载脂蛋白E(apolipoprotein E，apoE)基因启动子区—427C／T多态性与Alzheimer病(Alzheimer's disease，AD)发病风险的关系。方法 采用聚合酶链反应和限制性片段长度多态性方法，在104例AD患者和110名正常人中检测了apoE基因—427C／T各基因型及基因频率的分布。按比值比(odds ratio，0R)作疾病关联分析。结果 (1)AD患者与正常对照人群之间不存在—427C／T各等位基因和基因型频率分布的差异(P＞0．05)；(2)按apoE ε4基因分层后，无论是ε4型人群还是非ε4人群都不存在AD患者与正常老人间多态分布的差异(P＞0．05)；(3)在—427C／T 3种基因型中，仅T／T型AD与apoE ε4等位基因呈正关联(OR＝3．94，95％CI：2．206—7．038，x^2＝21．48，P＜0．05)。结论 上海地区汉族人群中，apo E基因—427C／T多态不是AD的疾病易感因子。     

2型糖尿病患者颈动脉粥样硬化与尿微量白蛋白的关系

目的探讨2型糖尿病患者颈动脉硬化与尿微量白蛋白的关系。方法收集109例2005年至2008年在本院住院的2型糖尿病患者,采用彩色多普勒超声诊断仪10MHz高频探头检测患者双侧颈动脉,按超声检查结果分为4组：颈动脉正常组30例[双侧颈动脉内膜中层厚度（CIMT）〈0．9mm];颈动脉内膜增厚组30例（0．9mm≤CIMT≤1．3mm）;稳定斑块组23例（斑块呈强回声,伴或不伴声影）;不稳定斑块组26例（斑块呈略低回声,内部或周边／有强回声附着）。同时测定血肌酐、空腹血糖（FPG）、糖化血红蛋白（HbA1c）、血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL）、高密度脂蛋白胆固醇（HDL）、尿微量白蛋白（MAU）,记录血压并计算体质量指数,比较四组患者MAU的差异。结果各组年龄、性别、体质量指数、血压、血肌酐比较差异无统计学意义（P〉0．05）,MAU值各组与CIMT〈0．9mm组间差异有显著性（P〈0．01）,尤其是不稳定斑块组与正常组差异最显著（P〈0．01）,不稳定斑块组与稳定斑块组、内膜增厚组,稳定斑块组与内膜增厚组差异也有统计学意义（P〈0．05）,不稳定斑块组与正常组在病程、FPG、Hba1C、TC、TG、LDL、HDL比较差异均有统计学意义（P〈0．05）,稳定斑块组与内膜增厚组除TC、MAU差异有统计学意义外（P〈0．05）,其余指标差异均无统计学意义（P〉0．05）。结论2型糖尿病患者颈动脉硬化程度与尿微量白蛋白水平呈正相关,MAU可预测2型糖尿病患者心血管疾病的风险。     

内皮型一氧化氮合酶基因G894T突变与中国人冠状动脉粥样硬化性心脏病的相关研究

目的 探讨内皮型一氧化氮合酶（endothelial nitric oxide synthase,e NOS）基因第7外显子G894T点突变与中国人冠状动脉粥样硬化性心脏病（简称冠心病）发病之间的关系。方法 应用聚合酶链反应技术，限制性内切酶分析和病例－对照方法，检测了108名中国汉族正常人，106例冠心病患者的eNOS基因G894T点突变频率。比较各组间的基因型频率与等位基因频率。结果 （1）中国汉族正常人eNOS基因G894T突变GG，GT，TT基因型频率分布为0.9095,0.0883和0.0021;G,T等位基因频率分别为0．9537和0．0463。（2）冠心病及其心肌梗塞亚组eNOS基因GT＋TT型频率分别为0．2219和0．2387，与GG型相比，均显著高于正常人（P＜0．05；冠心病组及心肌梗塞亚组T等位基因频率分别为0．1179和0．1275，均极显著高于正常人（P＜0．01。（3）冠状动脉造影确诊的冠心病患者eNOS基因G894T突变频率在单支，双支和多支病变组之间差异均无显著性（P＞0．05）。结论 eNOS基因G894T突变可能是中国人冠心病遗传易感性的基因标志之一。     

Effects of apoE gene polymorphism on Lp(a) concentrations depend on the size of apo(a): a study of 466 white men

 Polymorphisms in the genes for the low-density lipoprotein (LDL) receptor ligands, apolipoprotein E (apoE), and apolipoprotein B (apoB) are associated with variation in plasma levels of LDL cholesterol. Lp(a) lipoprotein(a) [Lp(a)] is LDL in which apoB is attached to a glycoprotein called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined isoforms differing in molecular weight, which are inversely correlated with Lp(a) concentrations in blood. The interaction of apo(a) with triglyceride-rich lipoproteins differs with the size of apo(a), and therefore the effects of apoE gene polymorphism on Lp(a) levels could also depend on apo(a) size. We have investigated the possible effect of genetic variation in the apoE and apoB genes on plasma Lp(a) concentrations in 466 white men with different apo(a) phenotypes. Overall there was no significant association between the common apoE polymorphism and Lp(a), but in the subgroup with apo(a)-S4, concentrations of Lp(a) differed significantly among the apoE genotypes (P=0.05). Lp(a) was highest in the apoE genotypes ɛ₂ɛ₃ and ɛ₃ɛ₃ and lowest in genotype ɛ₃ɛ₄, and the apoE polymorphism was estimated to account for about 2.4% of the variation in Lp(a). In contrast, in the subgroup with apo(a)-S2 Lp(a) was significantly lower (P=0.04) in apoE genotype ɛ₂ɛ₃ than in genotype ɛ₃ɛ₃. Lp(a) concentrations did not differ among the XbaI (P=0.65) or SP 24/27 (P=0.26) polymorphisms of the apoB gene. The expected effects of both apoE and apoB polymorphism on LDL levels were significant in the whole population sample and in subjects with large-sized apo(a) isoforms (P<0.01), whereas no effect was seen in those with low molecular weight apo(a) isoforms. We conclude that the influence of apoE genotypes on Lp(a) concentrations depends on the size of the apo(a) molecule in Lp(a), possibly because both apo(a)-S4 and apoE4 have high affinity for triglyceride-rich lipoproteins and may be taken up and degraded rapidly by remnant receptors. Received: 12 January 1995 / Accepted: 12 July 1996     

Apolipoprotein E phenotype and lipoprotein(a) in familial hypercholesterolaemia implication for lipoprotein(a) metabolism

The mechanisms regulating plasma levels of lipoprotein(a) [Lp(a)] are largely unknown. A two- to three-fold increase in Lp(a) levels in patients with familial hypercholesterolaemia (FH) has implied that LDL receptor activity may be an important factor in determining plasma Lp(a) levels, as it is in determining low-density lipoprotein (LDL) cholesterol concentration. Common apolipoprotein E (apoE) variants also affect plasma LDL cholesterol levels. We therefore examined the effect of the common apoE variants on plasma Lp(a) levels in 149 patients with heterozygous FH. Patients with the apoE₂ allele (n = 11) had significantly higher plasma levels of LDL cholesterol compared to those with a apoE₃E₃ phenotype, while patients with the apoE₄ isoform had similar levels. However, there was a significant effect of the apoE₂ allele in lowering Lp(a) levels, compared to the apoE₃E₃ group. The median Lp(a) concentration in patients possessing an apoE₂ isoform was 13.1 mg/dl below the median, while in those with an apoE₄ allele the median Lp(a) levels were 4.13 mg/dl higher. There was a marked inverse correlation between plasma Lp(a) and LDL cholesterol concentration in the FH patients carrying the apoE₂ allele. Our data imply that difference in Lp(a) levels observed between FH patients with different apoE isoforms does not result from altered clearance of Lp(a) via the LDL receptor pathway, and suggest that apoE mediated hepatic up-take, or conversion, of remnant particles may be determining Lp(a) production rate.Abbreviations apo apoprotein - CHD coronary heart disease - FH familial hypercholesterolaemia - HDL high-density lipoprotein - LDL low-density lipoprotein - Lp(a) lipoprotein(a)     

Lack of association of apolipoprotein E polymorphism with plasma Lp(a) levels in the Chinese

Apolipoprotein E (apoE) polymorphism and its influence on plasma lipids, lipoproteins, lipoprotein (a) [Lp(a)] and apolipoproteins was studied in 536 (270 males and 266 females) healthy Chinese in Singapore. From analysis of variance with age and BMI as covariates, apoE genotype was found to exert a significant influence on plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apoB in females. Its effect in males was marginally significant only on LDL-C. In both sexes, plasma TC, LDL-C and apoB were lower in those who were E2-3 than in those who were E3-3. There was no significant difference in log-transformed Lp(a) level between the apoE genotypes after adjusting for the confounding effect of LDL-C in addition to age and BMI. The percentage variance (R2times100) of the lipid traits explained by apoE polymorphism in the females was 4.94% for plasma TC, 5.85% for LDL-C and 4.25% for apoB. We conclude that: 1) ε2 allele had a lowering effect on plasma TC, LDL-C and apoB; 2) apoE polymorphism did not have any significant influence on Lp(a) concentration; and 3) the effect of apoE polymorphism on plasma TC, LDL-C and apoB was gender-specific, with a stronger influence in females than in males.     

Risk factor–gene interaction in carotid atherosclerosis: effect of gene polymorphisms of renin-angiotensin system

The risk factor–gene interaction in carotid atherosclerosis was investigated in 205 community-dwelling healthy subjects aged 50 years or more in Japan. The intima–media thickness (IMT) of the common carotid artery was evaluated by ultrasonography with a 7.5-MHz probe. Gene polymorphisms were determined for each subject with angiotensin-converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen (AGT) M235T, angiotensin II type 1 receptor (AT1R) A1166C, and apolipoprotein E (apoE) genotypes. There was no genotype-specific difference in carotid IMT among any genes examined. Combinations of genotypes did not increase carotid IMT compared with subjects without these genotypes. In the total population, multiple regression analysis showed that age, systolic blood pressure (SBP), sex, and body mass index (BMI) were significantly associated with carotid IMT. However, the association between risk factors and IMT was genotype-specific. Age was significantly associated with IMT in ACE D carriers, but not in subjects with the ACE II genotype. Analysis of covariance adjusted with other risk factors showed that the age-dependent change in IMT was significantly different between subjects with the ACE II genotype and the ACE D carriers (F[1.196] = 4.97; P = 0.027). Similarly, the regression of IMT on SBP was significantly different between AGT TT and AGT MT + MM (F[1.196] = 7.20; P = 0.0079). The regression of IMT on BMI was also significantly different between apo E4 carriers and noncarriers (F[1.196] = 6.78; P = 0.0099). Furthermore, general linear model analysis with risk factors, genotype, and risk factor-genotype interactions revealed that the age^*ACE genotype interaction, the SBP^*AGT genotype interaction, and the BMI^*apoE genotype interaction were significantly associated with IMT. These findings further support the role of risk factor-gene interaction in carotid atherosclerosis. Received: January 5, 2001 / Accepted: February 5, 2001     

Possible association between genetic variability at the apolipoprotein(a) locus and Alzheimer's disease in apolipoprotein E2 carriers

Apolipoprotein(a) (Apo(a)) is a glycoprotein that is linked by a disulfide bond to apolipoprotein B on low density lipoprotein particles to form lipoprotein(a) (Lp(a)). High plasma levels of Lp(a) are thought to contribute directly to the development of atherosclerosis. We tested a variant (T3888P) located in the Kringle-IV region of Apo(a) in a case-control series. Overall, there were no differences between case and controls. However, in the apoE2 positive subgroup, we noticed that the mutant allele is over-represented in the cases (P=0.005). We suggest that this polymorphism and others at the Apo(a) locus be further studied in relation to Alzheimer's disease.     

血浆前蛋白转化酶枯草溶菌素9 与钙化性主动脉瓣疾病的关联机制

目的:探讨血浆前蛋白转化酶枯草溶菌素9(PCSK9)与钙化性主动脉瓣疾病(CAVD)的相关性。方法:经心脏彩超筛选CAVD 患者120 例及阴性对照组患者40 例,通过CT 定量评分系统分4 组:AVC 1、2、3 和4 级,并通过软件计算主动脉瓣钙化积分。检测血浆总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、三酰甘油(TG)、载脂蛋白A1(Apo A1)及载脂蛋白B(Apo B)、脂蛋白(a){LP(a)}和高敏C 反应蛋白(hsCRP)水平以及PCSK9 水平。结果:4组患者LDL-C、Apo B 和Lp(a) 水平差异有显著性(P<0.05),AVC2-4 级患者明显高于AVC1 级,而TG、HDL-C、apo A1 和hsCRP 组间差异无统计学意义。AVC3 级和AVC 4 级的TC 水平高于AVC1 组(P<0.05)。同时,AVC2-4 组血浆PCSK9 水平高于AVC1 组(P<0.05)。将所有人群的主动脉瓣钙化积分与TC(r =0.248,P =0.026),LDL-C (r =0.222,P =0.048),Lp(a)(r =0.276,P =0.013),Apo A1(r =0.245,P =0.012),Apo B(r =0.212,P =0.019)和PCSK9(r =0.309,P =0.005)均存在明显相关性,ApoA1,Apo B 呈正相关。结论:CAVD 患者PCSK9 水平明显高于对照组,PCSK9 与CAVD 的发生存在相关性。     

Association of apoE gene polymorphisms with lipid metabolism in renal diseases

Background and ObjectivesApolipoprotein E (apoE) plays a central role in the metabolism and homeostasis of lipids. ApoE gene encodes three major isoforms: ε2, ε3 a nd ε4 forming six phenotypes: E2E2, E2E3, E2E4, E3E3, E3E3 and E4E4. Disorders of the lipid metabolism and the homeostasis are frequently coexist in renal diseases. The association between gene polymorphisms of apoE and lipid metabolism were not consistent. This meta-analysis was performed to assess the association between gene polymorphisms of apoE and lipid metabolism in renal diseases.MethodsA pre-defined literatures search and selection of eligible relevant investigations were performed to extract and collect data from electronic databases.ResultsSixteen articles were enrolled for the analysis of association between apoE gene polymorphisms and lipid metabolism. Subjects with E3E4 had a higher total cholesterol (TC) than those with E3E3, and subjects with E2E3 had a lower TC than those with E3E3. Subjects with ε2, had a lower TC than those with ε3 or ε4, and subjects with ε4 had a higher TC than those with, ε3. Subjects with E2E2, E2E3 or E4E4 had a higher triglyceride (TG) than those with E3E3. Subjects with ε4 had a higher TG than those with ε3. Subjects with ε2, had a higher level of TG than those with non-ε2. Subjects with E3E4 had a slightly lower high-density lipoprotein (HDL) than those with E3E3. E3E4 appeared to be associated with lower levels of HDL. Subjects with E2E2, E2E3 had a notably lower low-density lipoprotein (LDL) than those with E3E3. Subjects with ε2, had a lower LDL than those with ε3 or ε4 ApoE gene polymorphisms were not associated with very low-density lipoprotein, and lipoprotein (a) [Lp(a)]. Subjects with E2E3 or E2E4 had higher apoE levels than those with E3E3, and subjects with E4E4 had lower apoE levels than those with E3E3.ConclusionApoE gene polymorphisms are associated with the expression of TC, TG HDL, LDL, Lp(a) or apoE.     

Relationship of angiotensin-converting enzyme gene polymorphism to carotid wall thickness in middle-aged men

The insertion/deletion (I/D) polymorphism of the human angiotensin-converting enzyme (ACE) gene is a major determinant of circulating ACE levels. The D allele has been suggested to be a potent risk factor for coronary artery disease; however, the effect of the ACE gene on carotid atherosclerosis remains controversial. We therefore studied the relationship between the ACE gene I/D polymorphism and carotid artery intima-media thickness (IMT). A random sample of 300 men aged 50-59 years living in southern Finland were selected, and 233 agreed to participate (74%). Data were collected in 219 subjects. Quantitative B-mode ultrasonography was used to measure the maximum near and far wall IMT of right and left common, bifurcation, and internal carotid artery. The mean maximum IMT (overall mean) was calculated as the mean of 12 maximum IMTs at 12 standard sites. Patients with an IMT higher than 1.7 mm in at least one of 12 standard sites were assumed to have carotid atherosclerosis. The I/D polymorphism was determined by polymerase chain reaction. Overestimation of the frequency of the DD genotype was eliminated by insertion-specific primer and the inclusion of 5% dimethylsulfoxide. No significant differences were found in carotid wall thickness between the three genotypes; the overall mean IMT were 1.18 +/- 0.30, 1.22 +/- 0.24, and 1.08 +/- 0.40 mm in genotypes of II, ID, and DD, respectively. Similarly, the ACE genotypes and allele frequencies did not differ significantly between the subjects with and those without carotid atherosclerosis. There was no association in the subgroups among only nonsmoking subjects or subjects without chronic medication. The present data indicate that the I/D polymorphism of the ACE gene is not related to carotid IMT and is unlikely to play a major role in carotid atherosclerosis.