Polymorphisms in the apolipoprotein E gene regulatory region in relation to coronary heart disease and their effect on plasma apolipoprotein E.

In a previous study which examined the distribution of apolipoprotein E genotypes and plasma levels in a sample of male coronary heart disease (CHD) patients and controls, we found a significant excess of the genotypes carrying APOE*4 allele in CHD men (18.2%) vs. controls (9.6%) and an association between the APOE*4 allele and the lowest concentrations of apoE. In the present investigation, we re-examined in the same samples two recently identified polymorphisms in the promoter region of APOE, -491A/T and -427T/C, which may alter the level of apoE expression. No differences in the distributions of the -491A/T genotypes and alleles were observed between cases and controls (-491*A = 0.760 and 0.757 respectively). Polymorphism -427T/C showed in CHD patients an excess of -427*C allele (patients vs. controls = 0.123 vs. 0.074) and corresponding genotypes that was marginally significant. Stratification of the samples according to the presence/absence of APOE*4 showed that the excess of the -427*C allele concerned only CHD patients not carrying APOE*4 allele (patients vs. controls = 0.133 vs. 0.061; p=0.017). This result suggests that the presence of -427*C allele could represent a risk for developing CHD in subjects with E2/E2, E3/E2, and E3/E3 genotypes. Studies carried out on patients with Alzheimer's disease demonstrated that -491A/T and -427T/C polymorphisms affect the level of plasma apoE. In the present study, carried out on CHD patients and controls, the genetic variation at -427 and -491 sites of the APOE regulatory region had no apparent effect on apoE plasma concentration.     

Apolipoprotein E polymorphisms in Mexican patients with coronary artery disease.

BACKGROUND: Apolipoprotein E polymorphisms have important effects on plasma lipid levels and in the genetic susceptibility to development of cardiovascular diseases. Thus, the purpose of this study was to investigate the association of apolipoprotein E polymorphisms with coronary artery disease and with plasma lipid levels in a group of Mexican Mestizo patients. METHODS: Apolipoprotein E polymorphisms were determined in 156 Mexican patients with coronary artery disease and 200 non-related healthy controls using the restriction fragment length polymorphism technique. The correlation of these polymorphisms with lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides) in the patient group was determined. RESULTS: A similar distribution of allele and genotype frequencies in coronary artery disease patients and healthy controls was found. Higher serum levels of high-density lipoprotein cholesterol and lower levels of low-density lipoprotein cholesterol, triglycerides and glucose were found in patients with the APOE*2/3 genotype when compared to patients with the APOE*3/4 and APOE*3/3 genotypes, although these differences were not significant. CONCLUSIONS: Our data suggest that genetic variation at the APOE is not a genetic factor related to the genetic susceptibility to coronary artery disease in Mexican individuals, but the role of this polymorphism in determining the lipid profile cannot be excluded.     

Five polymorphisms in gene candidates for cardiovascular disease in Afro-Brazilian individuals

Associations of polymorphisms in the angiotensin I-converting enzyme (ACE), apolipoprotein B (APOB) and apolipoprotein E (APOE) genes with hypertension and variations in lipid serum levels were evaluated in 184 Afro-Brazilians with a familial history of coronary artery disease (CAD). ACE (Ins/Del) and APOB (Ins/Del, XbaI, and EcoRI) and APOE (HhaI) polymorphisms were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses on agarose, and polyacrylamide gel electrophoresis. Serum lipids were measured by means of routine enzymatic assays. The results showed a high frequency of hypertension (44%) in Afro-Brazilians that was increased in subjects >40 years old and those with a blood mass index (BMI) higher than 25 kg/m(2) (P<0.001). The ACE Del allele was associated with hypertension in men >40 years old (P<0.05). APOE (HhaI) and APOB (XbaI and Ins/Del) polymorphisms were not associated with hypertension or variations in serum concentrations of lipids, while subjects with the APOB E- allele had higher low-density lipoprotein cholesterol (LDL-C) levels than E+ carriers (P<0.05). These results suggest that ACE Ins/Del polymorphism is associated with hypertension, and APOB EcoRI polymorphism is associated with LDL-C variation in Afro-Brazilians.     

5' ins/del and 3' VNTR polymorphisms in the apolipoprotein B gene in relation to lipids and coronary artery disease.

BACKGROUND: Studies that considered apolipoprotein B (APOB) gene polymorphisms as risk factors for coronary artery disease (CAD) have reported conflicting results. We sought to analyze the association between 5' ins/del and 3' VNTR polymorphisms of APOB, lipid parameters and CAD risk. METHODS: We recruited 251 patients with CAD, documented by coronary angiography, and 94 controls. Genotyping was performed by PCR. Lipids and apolipoproteins were measured. RESULTS: 5' ins/del (ins/ins, ins/del, del/del) and 3' VNTR (LL, SS, LS) polymorphism frequencies were significantly (p<0.05) different between controls and CAD patients. LL and del/del were significantly associated with higher levels of apolipoprotein B (apoB), total cholesterol/high-density lipoprotein cholesterol ratio and apoB/apoA-I ratio (p<0.05) and with increased risk of CAD. The odds ratio for significant coronary stenosis associated with del/del was 3.2 (95% CI 1.6-36.42) (p=0.032) and with LL was 2.2 (95% CI 1.1-5.1) (p=0.042). CONCLUSIONS: The two polymorphisms exert an impact on lipid levels and contribute to the susceptibility to the development of CAD.     

Association of apolipoprotein E and B polymorphisms with serum lipids.

Genetic polymorphism of apolipoprotein E (apoE) and the Xbal restriction-fragment-length polymorphisms (RFLP) of the gene for apolipoprotein B (apoB) have both been shown to be associated with plasma lipid concentration. We studied the combined effect of these gene polymorphisms on serum cholesterol concentrations in 300 subjects aged nine to 18 years. In three way ANOVA, there was a statistically significant interaction between the effects of apoE phenotype and gender on serum cholesterol (P = 0.009). Therefore, males and females were analysed separately by two way ANOVA: there was no interaction between the effects of apoE phenotype and apoB Xbal polymorphism in either gender. In females, there were independent effects of both the apoE phenotype (P = 0.020) and the apoB Xbal genotype (P = 0.037) on serum cholesterol, but in males these effects were not statistically significant. These data suggest that variations at the apolipoprotein B and E gene locus play a role in the determination of serum cholesterol concentration in young female Finns.     

Genetic analysis of Indian subjects with clinical features of possible type IIa hypercholesterolemia

We performed genetic analysis in 55 patients with clinical features of possible type IIa hypercholesterolemia and 76 normolipemic healthy subjects for mutations and polymorphisms in the low-density lipoprotein (LDL) receptor (LDLR), apolipoprotein B-100 (APOB), apolipoprotein E (APOE), and hepatic lipase (LIPC) genes to elucidate the important genetic factors that can influence cholesterol levels in our population. None of the subjects showed mutations in part of exon 26 of the APOB gene, whereas two class 5 mutations were identified in exon 9 of the LDLR gene. First, an E387K mutation was observed in a Gujarati family in which both the parents were heterozygous for the mutation. Second, a L393R mutation was observed in a 38-year-old female. We found no correlation between LIPC -514C/T genotypes and cholesterol levels whereas the apoepsilon4 allele frequency was significantly higher in cases and the apoE4 genotype was found to influence total cholesterol levels.     

Association of Apolipoprotein E and B Polymorphisms with Serum Lipids

Genetic polymorphism of apolipoprotein E (apoE) and the Xbal restriction-fragment-length polymorphisms (RFLP) of the gene for apolipoprotein B (apoB) have both been shown to be associated with plasma lipid concentration. We studied the combined effect of these gene polymorphisms on serum cholesterol concentrations in 300 subjects aged nine to 18 years. In three way ANOVA, there was a statistically significant interaction between the effects of apoE phenotype and gender on serum cholesterol (P = 0.009). Therefore, males and females were analysed separately by two way ANOVA: there was no interaction between the effects of apoE phenotype and apoB Xbal polymorphism in either gender. In females, there were independent effects of both the apoE phenotype (P = 0.020) and the apoB Xbal genotype (P = 0.037) on serum cholesterol, but in males these effects were not statistically significant. These data suggest that variations at the apolipoprotein B and E gene locus play a role in the determination of serum cholesterol concentration in young female Finns.     

Familial dysbetalipoproteinemia associated with apolipoprotein E3-Leiden in an extended multigeneration pedigree.

By the careful screening of familial dysbetalipoproteinemic (FD) patients, five probands showing heterozygosity for the APOE*3-Leiden allele were found. Genealogical studies revealed that these probands share common ancestry in the 17th century. In a group of 128 family members, spanning three generations, 37 additional heterozygous APOE*3-Leiden gene carriers were detected. Although with a variable degree of severity, all carriers exhibited characteristics of FD such as (a) elevated levels of cholesterol in the very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) fractions, (b) elevated ratios of cholesterol levels in these density fractions over total plasma levels of triglycerides, and (c) strongly increased plasma levels of apolipoprotein E (apoE). Multiple linear regression analysis revealed that most of the variability in expression of FD in APOE*3-Leiden allele carriers can be explained by age. Body mass index showed a less significant influence on the expression of FD. Gender had no effect on the expression in E*3-Leiden allele carriers, nor did it influence the age of onset of FD. In the group of APOE*3-Leiden allele carriers, we found that the E*2 allele enhances the expression of FD, whereas the E*4 allele had the opposite effect. Isoelectric focusing of plasma and of isolated VLDL, IDL, and high density lipoprotein density fractions showed that in E*3-Leiden allele carriers the apoE3-Leiden variant largely predominates over its normal apoE counterpart, especially in the VLDL and IDL density fractions. We conclude that in APOE*3-Leiden allele carriers FD is dominantly inherited with a high rate of penetrance, i.e., the presence of normally functioning apoE molecules in the plasma does not prevent the age-related expression of this disease.     

Association between apolipoprotein E polymorphism and coronary artery disease in the Kermanshah population in Iran

OBJECTIVE: Coronary artery disease (CAD) is the major cause of death in developing countries, such as Iran. The apolipoprotein E gene (APOE) is considered an important genetic determinant of CAD. In this study, the relationship between APOE polymorphism with lipid variation in CAD patients in Kermanshah, Iran was investigated. METHODS: This case-control study consisted of 115 CAD patients who angiographically had at least 30% stenosis and 135 unrelated controls. APOE polymorphism was detected by PCR-RFLP and serum lipid level was measured enzymatically. RESULTS: The APOE-epsilon4 and -epsilon2 allele frequencies were significantly higher in the CAD patients than in the control group (P < 0.001). The CAD patients with epsilon3/epsilon4 genotype had also higher TC (P < 0.001) and LDL-C (P < 0.01) and lower HDL-C (P < 0.03) levels than that of the control group. CONCLUSIONS: APOE-epsilon4 allele is a risk factor for CAD, so that carriers of this allele with high levels of LDL-C may be susceptible to CAD and myocardial infarction.     

Variable expression of familial dysbetalipoproteinemia in apolipoprotein E*2 (Lys146-->Gln) Allele carriers.

Genetic and biochemical studies were carried out in 96 relatives of six independently ascertained probands with familial dysbetalipoproteinemia (FD) carrying the APOE*2 (Lys146-->Gln) allele. Compared to noncarriers, the 40 heterozygous APOE*2 (Lys146-->Gln) allele carriers exhibited markedly increased mean levels of cholesterol and triglyceride in the very low density lipoproteins (VLDL) (1.89 +/- 0.37 vs 0.30 +/- 0.27 and 1.86 +/- 0.37 vs 0.68 +/- 0.27 mmol/liter, respectively) and plasma apolipoprotein (apo) E levels (28.1 +/- 1.6 vs 4.6 +/- 1.1 mg/dl), which is characteristic for FD. By means of a pedigree-based maximum likelihood method we calculated that carrier-status accounted for 57% and 71%, respectively, of the total variance of the ratio (VLDL + IDL)-cholesterol/plasma triglyceride and plasma apoE levels. APOE*2 (Lys146-->Gln) and APOE*3-Leiden allele carriers were found to differ significantly in: (a) plasma apoE levels, (b) in the amounts of triglycerides in the VLDL and VLDL + IDL fraction, and (c) in the amount of cholesterol in the VLDL and VLDL + IDL fraction relative to the amount of triglyceride in these fractions. In the APOE*2 (Lys146-->Gln) allele carriers the VLDL and VLDL + IDL fraction is relatively rich in triglycerides as compared with that in APOE*3-Leiden carriers. We hypothesize that these two rare mutations of apoE both lead to dominantly inherited forms of FD along different underlying metabolic defects.     

Associations of apolipoprotein E exon 4 and lipoprotein lipase S447X polymorphisms with acute ischemic stroke and myocardial infarction.

BACKGROUND: Because apolipoprotein E (apoE) and lipopoprotein lipase (LPL) polymorphisms interact with each other and with other factors to affect lipid metabolism, we sought to determine their separate and combined effects in association with ischemic vascular disease. METHODS: We performed a case-control study of 816 subjects: 246 acute ischemic stroke patients, 234 acute myocardial infarction patients, and 336 controls. APOE exon 4 and LPL S447X genotypes were determined. RESULTS:APOE epsilon2 and epsilon4 homozygotes were increased in stroke (4.5% vs. 1.0%, p = 0.008), while in myocardial infarction the epsilon4 allele was increased (12.6% vs. 9.5%, p = 0.006) but epsilon2 was decreased (3.7% vs. 12.1%, p = 0.000006). For subjects with either APOE epsilon2 or epsilon4 alleles, LPL X alleles were increased in vascular disease (OR = 2.2, p = 0.01). LPL X alleles displayed opposite tendencies toward association with disease when subjects were divided by sex, smoking, or APOE genotype. Meta-analysis and regression analysis of previous studies supported the sex and smoking dichotomies. CONCLUSION: This is the first report of an association of vascular disease with an interaction of APOE exon 4 and LPL S447X genotypes. Therefore, APOE genotypes and LPL S447X interactions with apoE, sex, and smoking may affect the risk of myocardial infarction and ischemic stroke.     

Abnormalities in apolipoprotein and lipid levels in an HIV-infected Brazilian population under different treatment profiles: the relevance of apolipoprotein E genotypes and immunological status.

HIV infection is associated with disturbances in lipid metabolism due to a host's response mechanism and the current antiretroviral therapy. The pathological appearance and progression of atherosclerosis is dependent on the presence of injurious agents in the vascular endothelium and variations in different subsets of candidate genes. Therefore, the Hha I polymorphism in the apolipoprotein E gene was evaluated in addition to triglycerides, total cholesterol, very low-density lipoprotein (VLDL), LDL, high-density lipoprotein (HDL), and apolipoprotein (apo) Al, B and E levels in 86 Brazilian HIV-infected patients and 29 healthy controls. The allele frequency for apoE in the HIV-infected group and controls was in agreement with data on the Brazilian population. Dyslipidemia was observed in the HIV group and verified by increased levels of triglycerides, VLDL and apoE, and decreased levels of HDL and apoAl. The greatest abnormalities in these biochemical variables were shown in the HIV-infected individuals whose immune function was more compromised. The effect of the genetic variation at the APOE gene on biochemical variables was more pronounced in the HIV-infected individuals who carried the apoE2/3 genotype. The highly active anti-retroviral therapy (HAART)-receiving group presented increased levels of total cholesterol and apoE. Dyslipidemia was a predictable consequence of HIV infection and the protease inhibitors intensified the increase in apoE values.     

The presence of apolipoprotein epsilon4 and epsilon2 alleles augments the risk of coronary artery disease in type 2 diabetic patients

OBJECTIVE: It has been suggested that there is a relationship between apolipoprotein E polymorphism and the severity of coronary artery disease in type II diabetes mellitus (T2DM). The current study specifically aimed to examine whether APOE polymorphism in association with serum lipids-lipoproteins level is a risk factor for developing coronary artery disease (CAD) in diabetic patients living in western of Iran. METHODS: The APOE genotypes were detected by PCR-RFLP in 152 angiographically documented diabetic CAD patients, 262 non-diabetic (ND) individuals with CAD and 300 unrelated controls (normal coronary artery cases without diabetes) and serum lipid level was measured enzymatically. RESULTS: The APOE-epsilon4 and epsilon2 allele frequencies were significantly higher in the CAD/T2DM and CAD/ND patients than in the control group (p<0.001). Our study demonstrated a significant association between APOE polymorphism and the level of plasma lipids with CAD/T2DM (p=0.001) and CAD/ND (p=0.026) patients. The CAD subjects with T2DM and ND patients carrying APOE-epsilon4 allele had lower plasma HDL-C level (p<0.001), (p=0.008) but had higher plasma LDL-C (p=0.01), total cholesterol (p=0.002), (p=0.03) and TG (p<0.001), (p=0.042) than that of the APOE-epsilon3 carriers, respectively. However, carriers of APOE-epsilon2 had significantly higher levels of plasma TG only. OR of APOE-epsilon4 and epsilon2 alleles in CAD/T2DM and CAD/ND patients were found to be 2.98 (p=0.001),1.86 (p=0.001), 2 (p=0.001), and 1.65 (p=0.001), respectively. CONCLUSIONS: The major finding of the present case-control study is that T2DM patients carrying APOE-epsilon2 and epsilon4 alleles have a higher risk of developing CAD than ND patients in the western population of Iran, with APOE-epsilon4 being more closely associated with CAD than the APOE-epsilon2 allele. These results indicated that carriers of APOE-epsilon4 allele have a distinct plasma lipids profile and carrier of this allele with low levels of HDL-C and with high levels of LDL-C may be susceptible to CAD and myocardial infarction specially in diabetic patients. This suggests that a therapeutic modality should be considered for these patients.     

Association of the apolipoprotein B gene polymorphisms with cholesterol levels and response to fluvastatin in Brazilian individuals with high risk for coronary heart disease.

The influence of genetic polymorphism of the apolipoprotein B on lipid metabolism and coronary heart disease (CHD) risk has been demonstrated in different populations, but few studies have shown the contribution of this risk factor in individuals from Brazil. The Ins/del, Xbal and EcoRI polymorphisms of apo B were evaluated in 93 controls and in 104 Caucasian individuals presenting with a high risk lipid profile (HR1) for CHD; 54 of these subjects (HR2) were treated with fluvastatin during 16 weeks. DNA polymorphisms of the apo B gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism. The X(-)X(-) genotype for Xbal polymorphism was associated with higher serum concentrations of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) (p<0.01) in women of the HR1 group. The Ins/del and EcoRI polymorphisms were not associated with variation of lipid profile. After treatment with fluvastatin, TC and LDL-C levels of HR2 individuals were reduced by 23% and 30%, respectively. Individuals with II genotype had significantly greater reduction (34%) of LDL-C than those with ID/DD genotypes (27%). These results indicate that the Xbal polymorphism is associated with variation of serum TC and LDL-C levels in Brazilian women with lipid profile of risk for CHD and the Ins/del polymorphism is associated with the therapeutic response to fluvastatin.     

Synergistic effect between apolipoprotein E and angiotensinogen gene polymorphisms in the risk for early myocardial infarction

BACKGROUND: Several studies based on different populations worldwide have described an association between cardiovascular diseases and genetic variations in the apolipoprotein E (A:POE), angiotensinogen (A:GT), angiotensin receptor type 1 (A:T1R), and angiotensin-converting enzyme (A:CE) genes. In addition, there is growing evidence of an interaction between hypercholesterolemia and the renin-angiotensin system in the risk for hypertension and atherosclerosis. METHODS: To determine whether the DNA polymorphisms in A:POE (epsilon2, epsilon3, and epsilon4 alleles), A:GT (M235T), A:T1R (1166 A:/C:), and ACE (I:/D:) are associated with early onset of myocardial infarction (MI), we genotyped 220 patients and 200 controls <55 years of age. Patients and controls were males from the same homogeneous Caucasian population. Data concerning hypertension, diabetes, and tobacco consumption were recorded. The lipid profiles of patients and controls were also determined. RESULTS: APOE, ACE, AGT, and AT1R allele and genotype frequencies did not differ between patients and controls. None of these polymorphisms was related to the biochemical values in patients or controls. The frequency of individuals who were both APOE epsilon4 allele carriers and AGT-TT homozygotes was significantly higher in patients than in controls (11% vs 3.5%; P: = 0.0037). In patients, the frequency of epsilon4 carriers was significantly higher (P: <0.00001) in those who were AGT-TT (46%) than those who were AGT-MT/MM (14%). Mean cholesterol was significantly higher in AGT-TT + APOE epsilon34/44 patients than in the TM/MM + epsilon34/44 or TT + epsilon23/33 genotypes (P: = 0. 029). CONCLUSIONS: Our data suggest a synergistic effect between the APOE and AGT polymorphisms and early MI. The increased risk could be mediated in part through higher cholesterol concentrations among individuals who are AGT-TT + APOE epsilon4 allele carriers.     

Effects of apolipoprotein E genotypes and other risk factors on the development of coronary artery disease in Southern Turkey

BACKGROUND: Apolipoprotein E (apoE) plays a major role in lipoprotein metabolism and lipid transport. Associations between apoE genotypes, coronary artery disease (CAD) and other risk factors have been described by many investigators. The aim of this study was to investigate the role of apoE gene polymorphism and other risk factors in the development of CAD in subjects whose coronary arteries were evaluated by means of coronary angiography. METHODS: The study population consisted of 199 subjects (114 male and 55 female). Of the total, 107 had CAD. The apoE gene was amplified by polymerase chain reaction (PCR) and then digested by CfoI restriction enzyme. The plasma lipid levels and other risk factors were also determined in all subjects. RESULTS: The epsilon2 and epsilon4 allele frequencies and genotypes carrying epsilon4 allele were significantly higher in CAD (+) patients. Plasma lipids except triglycerides were increased in CAD (+) cases. We found that apoE genotypes, HT, DM, male gender, age and smoking were the independent predictors of CAD. There was no association between apoE alleles and lipids. CONCLUSION: We conclude that apoE polymorphism (presence of epsilon4 allele) is associated with the development of CAD in Southern Turkey. In our study, we did not observe any effect of apoE alleles on lipid levels.     

The common polymorphism of apolipoprotein E: geographical aspects and new pathophysiological relations.

Apolipoprotein E (apoE) has important functions in systemic and local lipid transport, but also has other functions. The gene (APOE) shows a common polymorphism with three alleles--APOE*2, APOE*3, and APOE*4. Their frequencies vary substantially around the world, but APOE*3 is the most common almost everywhere and is often considered to be the ancestral or "wild-type" allele for that reason. However, there are several arguments for APOE*4 being the ancestral allele. But then, why has APOE*3 become so frequent? And why has APOE*4 not become extinct? The proportion of APOE*4 carriers increases from only 10-15% in southern Europe to 40-50% in the north. The gradient may be a trace of the demic expansion of agriculture that began about 10,000 years ago, but it may also reflect the possibility that APOE*4 carriers are less likely to develop vitamin D deficiency. The common APOE polymorphism is associated with varying risk of cardiovascular disease and Alzheimer's disease, but other interesting aspects may emerge in the future.     

Influence of apolipoprotein E polymorphism on serum lipid and lipoprotein changes: a 21-year follow-up study from childhood to adulthood. The Cardiovascular Risk in Young Finns Study.

BACKGROUND: We examined the influence of apolipoprotein E (apoE) polymorphism on longitudinal changes in serum lipids by following the subjects participating in The Cardiovascular Risk in Young Finns Study over a 21-year period. METHODS: Serum lipids were determined in randomly selected Finnish children and adolescents in 1980 and the subjects were re-examined in 1983, 1986 and after 21 years in 2001. ApoE polymorphism was determined in 1736 participants, and serum lipid values and apoE phenotypes were available for 1233 subjects. RESULTS: ApoE phenotype-related differences in serum total and low-density lipoprotein (LDL)-cholesterol were maintained throughout the 21-year follow-up from childhood to adulthood, i.e., the apoE epsilon2 allele was consistently associated with lower and the epsilon4 allele with higher total and LDL-cholesterol (p<0.001 for all). In adulthood, there was also a significant apoE phenotype-related difference in high-density lipoprotein (HDL)-cholesterol (p=0.007), and the epsilon2 allele was associated with higher and the epsilon4 allele with lower apoA-I and HDL-cholesterol. In addition, apoB increased in the phenotype order E3/2相似文献   

Apolipoprotein E polymorphism--a risk factor for metabolic syndrome.

BACKGROUND: Metabolic syndrome is closely related to several disturbances in lipid and lipoprotein metabolism. The aim of this study was to determine the association between apolipoprotein E (apoE) genotypes and the risk of metabolic syndrome and/or coronary heart disease complications. METHODS: The study included 279 subjects divided into three groups: 1) control subjects, 2) metabolic syndrome patients, and 3) obese patients with coronary heart disease. All subjects were characterized by body mass index, and plasma levels of glucose, triglycerides, cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). ApoE genotypes were identified by PCR-restriction fragment length polymorphism using genomic DNA. RESULTS: Statistical analysis of plasma parameters showed that subjects in groups 2 and 3 had higher levels of triglycerides and lower levels of HDL-C compared to group 1. The frequencies of apoE genotypes determined in this Romanian population (65% for E3/3, 19.6% for E4/3, 9.5% for E3/2, 4.1% for E2/2, 0.6% for E4/4, 1.3% for E4/2) were in agreement with those reported for other Caucasian populations. The distribution of apoE alleles indicated a higher frequency of epsilon4 in groups 2 and 3. There was a higher frequency of the apoE4/3 genotype in groups 2 and 3, which was significantly correlated with higher levels of triglycerides and lower levels of HDL-C. CONCLUSIONS: Correlations of apoE genotypes with these markers indicate that the epsilon4 allele is an independent risk factor for metabolic syndrome.     

Genetic risk factors and ischaemic cerebrovascular disease: role of common variation of the genes encoding apolipoproteins and angiotensin-converting enzyme

DNA polymorphisms in genes encoding apolipoproteins (apo) A-I, C-III, B and E and angiotensin-converting enzyme (ACE) have been proposed to be associated with the risk of coronary artery disease (CAD). We studied whether the same genetic markers would also be associated with the occurrence and extent of atherosclerosis in cervical arteries. DNA samples from 234 survivors of stroke or a transient ischaemic attack aged 60 years or less were examined. The presence of atherosclerosis was assessed using aortic arch angiograms. The SstI polymorphism of apoA-I/C-III gene locus, the Xbal polymorphism of apoB gene, common apoE phenotypes and the insertion/deletion polymorphism of the ACE gene were analysed. The allele frequencies of the apoA-I/C-III, apoB, apoE or ACE gene did not differ between the groups with (n = 148) or without (n = 85) cervical atherosclerosis. However, when patients with at least one apoE4 allele and one X2 allele of apoB were combined and compared with those without either of them (E2E3 or E3E3 and X1X1), a significant association with the presence of cervical atherosclerosis was found (P = 0.03). The patients having the E2E3 phenotype had a significantly elevated serum triglyceride level compared with those with the E3E3 phenotype (P = 0.03). Serum high-density lipoprotein (HDL) cholesterol was lower in the patients with the E2E3 phenotype than in those with the E3E3 and E3E4 (P = 0.01 and P = 0.06, respectively). The apoB or ACE genotypes were not significantly associated with serum lipid or lipoprotein levels. There was no association between the ACE gene polymorphism and the occurrence of hypertension. In conclusion, the interaction of common apoB and apoE alleles may increase the risk of atherosclerosis in cervical arteries.