Is ε4 allele of apolipoprotein associated with more severe end‐organ damage in essential hypertension?

The aim of the present study comparing patients with mild to moderate hypertension with controls, was to explore a possible association between hypertension-related target organ damage and evaluation found in the gene encoding apolipoprotein E (apo E) genotype. Detailed medical history was recorded and physical examination was performed for all patients in the study (88 hypertensives, 63 normotensive controls). PCR (Polymerase Chain Reaction), RFLP (Restriction Fragment Length Polymorphism), and agarose gel electrophoresis techniques were used to determine the apo E genotypes. The frequencies of apo epsilon2, apo epsilon3, and apo epsilon4 alleles were 3.97, 88.06, and 9.95%, respectively in the hypertensive group. The frequencies of apo epsilon2, apo epsilon3, and apo epsilon4 alleles were 5.5, 92.0, and 2.38%, respectively in the control group. There were about twice as many individuals in the heterozygote hypertensive group who had apo E3/4 as compared to the control group (7.30 vs. 2.38%) (p = 0.07). The hypertensive patients who were carriers of the apo epsilon4 had significantly higher organ damage (left ventricular hypertrophy (p < 0.001). dilated left atrium (p < 0.05), retinopathy (p < 0.05)) as compared to those who were not carriers of apo epsilon4. These results showed a trend for the epsilon4 allele to be associated with a higher prevalence of target organ damage in patients with mild to moderate hypertension.     

Apolipoprotein E: risk factor for Alzheimer disease.

The apolipoprotein E gene (APOE) has three common alleles (epsilon 2, epsilon 3, and epsilon 4) that determine six genotypes in the general population. In this study, we examined 77 patients with late-onset Alzheimer disease (AD), along with an equal number of age- and sex-matched controls, for an association with the APOE-epsilon 4 allele. We show that the frequency of this allele among AD patients was significantly higher than that among the control population (.351 vs. .130, P = .000006). The genotype frequencies also differed between the two groups (P = .0002), with the APOE-epsilon 4/epsilon 3 genotype being the most common in the AD group and the APOE-epsilon 3/epsilon 3 being the most common in the control group. In the AD group, homozygosity for epsilon 4 was found in nine individuals, whereas none was found in the control group. The odds ratio for AD, when associated with one or two epsilon 4 alleles, was 4.6 (95% confidence interval [CI] 1.9-12.3), while the odds ratio for AD, when associated with heterozygosity for APOE-epsilon 4, was 3.6 (95% CI 1.5-9.8). Finally, the median age at onset among the AD patients decreased from 83 to 78 to 74 years as the number of APOE-epsilon 4 alleles increased from 0 to 1 to 2, respectively (test for trend, P = .001). Our data, which are in agreement with recent reports, suggest that the APOE-epsilon 4 allele is associated with AD and that this allelic variant may be an important risk factor for susceptibility to AD in the general population.     

Polymorphism of the apolipoprotein E gene and the risk of myocardial infarction

The apolipoprotein E (ApoE) gene polymorphism resulting from nucleotide substitutions in exon 4 was analyzed in Russian and Tatar patients with myocardial infarction (MI) from Bashkortostan. Alleles epsilon 2, epsilon 3, and epsilon 4 were identified by PCR. The genotype frequency distribution proved to be age-dependent in healthy Russians, genotype E2/3 increasing in frequency in subjects beyond 45. Russians who suffered MI under 45 had lower frequencies of genotype E3/3 (50.00% vs. 75.47% in controls of the same age, P = 0.013, OR = 0.33) and allele epsilon 3 (72.12% vs. 85.85%, P = 0.020, OR = 0.43) and a higher frequency of allele epsilon 4 (22.12% vs. 10.38%, P = 0.030, OR = 2.45). Russians who suffered MI complicated by cardiogenic shock (CS) had a significantly higher frequency of genotype E3/4 and lower frequencies of genotype E3/3 and allele epsilon 3 as compared with MI patients without CS. In Tatars, genotype E4/4 occurred at a frequency of 14.29% in patients who suffered MI under 45, and was not detected in healthy subjects of the same age (P = 0.024, OR = 17.85). Thus, the ApoE polymorphism was associated with higher risk of MI in Russians and Tatars under 45.     

Genetic association between the apolipoprotein E (ApoE) gene alleles and various forms of Alzheimer's disease]

Allele epsilon 4 of the apolipoprotein E (APOE) gene is associated with higher risk of Alzheimer's disease (AD) in many, though not all, ethnic groups. The APOE allele and genotype frequency distributions were studied in 207 AD patients without cerebrovascular disorders, 62 AD patients with cerebrovascular disorders (combined AD), and 206 control individuals (ethnic Russians from the Russian population). The frequency of allele epsilon 4 in patients with early-onset and late-onset AD was three times higher than in control individuals (p < 0.000001). Compared with control people, patients with cerebrovascular disorders displayed a twofold higher frequency of allele epsilon 4; the difference between the two groups was significant (p = 0.0019). Relative risk of AD in carriers of allele epsilon 4 was five times higher than in carriers of alleles epsilon 2 and epsilon 3 (p < 0.000001). Allele epsilon 2 had a protective effect with respect to AD onset until 65 years of age (p = 0.015). Thus, APOE allele epsilon 4 proved to be a universal factor of early-onset, late-onset, and combined AD in ethnic Russians from Russia.     

Apo E gene polymorphism on development of diabetic nephropathy

Type 2 diabetes causes premature morbidity and mortality due to the complications of atherosclerosis and diabetic nephropathy (DN). Polymorphism of Apo E gene is known to influence lipid metabolism. Apo E is polymorphic, consisting of three common isoforms (epsilon2, epsilon3 and epsilon4) encoded by three alleles (2, 3 and 4) in exon 4 on chromosome 19. The aim of this study was to investigate the effect of Apo E polymorphism as a prognostic risk factor for the development of DN. A total of 108 NIDDM patients were recruited from the Nephrology and Endocrinology Departments of our hospital. All subjects were divided into three groups: Group I: diabetes with nephropathy (n:37), group II: diabetes without nephropathy (n:71), group III: controls (n:46). Apo E genotypes were determined by real-time PCR. The epsilon4 allele frequency was significantly higher in-group I (10.8%) than in-group III (2.2%), (p < 0.05). In diabetics without nephropathy, the total cholesterol and LDL cholesterol levels were significantly lower in subjects with epsilon2 alleles than epsilon3 and epsilon4 alleles. In conclusion, the present prospective study indicates that the epsilon4 allele of the Apo E polymorphism is one of the prognostic risk factors involved in the development of DN with type 2 diabetes mellitus.     

Polymorphic gene markers of lipid metabolism are associated with diabetic nephropathy in patients with type 1 diabetes mellitus

In groups of type 1 diabetes mellitus patients with and without clinical signs of diabetic nephropathy (n = 62 and n = 68, respectively), a search was made for associations between diabetic nephropathy and the polymorphic marker epsilon2/epsilon3/epsilon4 of apolipoprotein E gene (APOE), I/D marker of apolipoprotein B gene (APOB), and Ser447Ter marker of lipoprotein lipase-encoding gene (LPL). The risk of diabetic nephropathy was higher in the carriers of allele epsilon3 and genotype epsilon3/epsilon3 of the polymorphic marker epsilon2/epsilon3/epsilon4 of APOE gene as well as in the carriers of allele 1 and APOB genotype/gene (OR = 2.08 and 2.16; 1.91 and 2.11, respectively). Conversely, the carriers of allele D showed a reduced risk of this complication (OR = 0.52). No significant differences in distribution of alleles and genotypes of the polymorphic marker Ser447Ter of LPL gene were found between the groups. Our results indicate that the genes encoding two major components of lipid metabolism are involved in the development of diabetic nephropathy in patients with type 1 diabetes mellitus.     

Apolipoprotein E and apolipoprotein CI polymorphisms in the Czech population: almost complete linkage disequilibrium of the less frequent alleles of both polymorphisms

Apolipoproteins E and CI are the predominant components of triglyceride-rich lipoproteins. The genes are located in one gene cluster and both are polymorphic. Three allelic (epsilon2, epsilon3 and epsilon4) polymorphisms of the APOE gene influence plasma cholesterol levels. The distribution of these alleles differ between ethnic groups. PCR genotyping was used to determine the APOE and APOCI allele incidence in a representative group of 653 probands (302 men and 351 women) of Czech origin. The observed relative frequencies for the epsilon2, epsilon3 and epsilon4 alleles were 7.1 %, 82.0 % and 10.9 %, respectively, and are similar to other middle European populations. APO epsilon4 carriers have the highest and APO epsilon2 carriers the lowest levels of plasma total cholesterol (p<0.0001) and LDL cholesterol (p<0.0001). The frequency of the insertion (I) allele (HpaI restriction site present) of the APOCI polymorphism was 18.5 %. APOCI I/I homozygotes have the highest level of triglycerides (p<0.003). An almost complete linkage disequilibrium of the insertion allele of APOCI with the APOE alleles epsilon2 and epsilon4 has been detected and suggests that the deletion in the APOCI gene probably follows the deriving of all three APOE alleles on the APO epsilon3 allele background.     

Effects of apolipoprotein E genotype on blood lipid composition and membrane platelet fluidity in Alzheimer's disease.

The blood lipid composition (plasma, platelets and leukocytes), platelet membrane fluidity, apolipoproteins A and B in the plasma of AD patients and control subjects with distinct Apo E genotypes were investigated. No significant differences were found between the Apo E genotype and the cholesterol, phospholipids, triglycerides and Apo B levels in the plasma; cholesterol and phospholipids levels in platelet and leukocyte membranes; and platelet membrane fluidity of AD and control groups. However, the phospholipid levels in the leukocyte membranes of the control subgroup with the genotypes epsilon3/epsilon3 and epsilon3/epsilon4 and the AD subgroups with the genotypes epsilon2/epsilon3 and epsilon3/epsilon3, epsilon3/epsilon4 and epsilon4/epsilon4 were significantly lower than those observed in the control subgroup with the genotype epsilon2/epsilon3. Moreover, the cholesterol and phospholipid levels in the platelet membranes of the AD subgroup with the epsilon2 allele were significantly higher than those in the AD subgroup without the epsilon2 allele and the control subgroups with and without the epsilon2 allele. A strong correlation was found between cholesterol and phospholipids levels in the platelet membranes of the AD and control subgroups without the epsilon2 allele, but the residual cholesterol level in the platelet membranes of the AD subgroup was twice that observed in the control subgroup. Furthermore, the Apo A levels in the plasma of the AD subgroup with the epsilon3 allele were significantly lower than those observed in the AD subgroup without the epsilon3 allele and the control subgroup with the epsilon3 allele. The results are discussed in terms of involvement of lipid metabolism in the etiopathogenesis of AD.     

Apolipoprotein E polymorphism influences postprandial retinyl palmitate but not triglyceride concentrations.

To quantify the effect of the apolipoprotein (apo) E polymorphism on the magnitude of postprandial lipemia, we have defined its role in determining the response to a single high-fat meal in a large sample of (N = 474) individuals taking part in the biethnic Atherosclerosis Risk in Communities Study. The profile of postprandial response in plasma was monitored over 8 h by triglyceride, triglyceride-rich lipoprotein (TGRL)-triglyceride, apo B-48/apo B-100 ratio, and retinyl palmitate concentrations, and the apo E polymorphism was determined by DNA amplification and digestion. The frequency of the apo E alleles and their effects on fasting lipid levels in this sample were similar to those reported elsewhere. Postprandial plasma retinyl palmitate response to a high-fat meal with vitamin A was significantly different among apo E genotypes, with delayed clearance in individuals with an epsilon 2 allele, compared with epsilon 3/3 and epsilon 3/4 individuals. In the sample of 397 Caucasians, average retinyl palmitate response was 1,489 micrograms/dl in epsilon 2/3 individuals, compared with 1,037 micrograms/dl in epsilon 3/3 individuals and 1,108 micrograms/dl in epsilon 3/4 individuals. The apo E polymorphism accounted for 7.1% of the interindividual variation in postprandial retinyl palmitate response, a contribution proportionally greater than its well-known effect on fasting LDL-cholesterol. However, despite this effect on postprandial retinyl palmitate, the profile of postprandial triglyceride response was not significantly different among apo E genotypes. The profile of postprandial response was consistent between the sample of Caucasians and a smaller sample of black subjects. While these data indicate that the removal of remnant particles from circulation is delayed in subjects with the epsilon 2/3 genotype, there is no reported evidence that the epsilon 2 allele predisposes to coronary artery disease (CAD). The results of this study provide not only a reliable estimate of the magnitude of the effect of the apo E polymorphism on various measurements commonly used to characterize postprandial lipemia, but also provide mechanistic insight into the effects of the apo E gene polymorphism on postprandial lipemia and CAD.     

Association of methylenetetrahydrofolate (MTHFR) and apolipoprotein E (apo E) genotypes with homocysteine, vitamin and lipid levels in carotid stenosis

The aim of the study was to investigate the association between methylenetetrahydrofolate (MTHFR) genotypes and levels of homocysteine (Hcy), folate, vitamin B12 and lipids as well as the association between apolipoprotein E (apo E) genotypes and levels of lipids in a Croatian healthy control group and a group of patients with > 70% carotid stenosis (CS). The study included 98 Croats, 38 patients with > 70% carotid stenosis and 60 age- and sex-matched controls. The MTHFR and apo E genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), Hcy by enzyme immunoassay, vitamins by immunochemiluminiscence, and lipids by spectrophotometric method. There was no difference between control subjects and CS patients in the distribution of C677T MTHFR genotypes (p=0. 786) and alleles (p=0.904), however, differences in the frequencies of apo E genotypes (p=0.012) and alleles (p=0.029) were statistically significant. The odds ratio for apo E 3/4 genotype was 3.93 (95% CI 1.23-12.61). Hyperhomocysteinemia (> or =15 micromol/L) was found in 11% of CS patients and 5% of control subjects. Total cholesterol, triglycerides, vitamin B12 and folate were statistically different in "all MTHFR genotypes" (p<0.001, p<0.01, p=0.044 and p=0.036, respectively), and in TC/TT (p<0.001, p=0.003, p=0.030 and p=0.032, respectively) groups. The levels of total cholesterol, LDL cholesterol and triglycerides in the apo E 3/3, and total cholesterol in the apo E 3/4 group yielded statistical difference. An association was found of apo E 3/4 genotype but not of MTHFR genotypes with the risk of CS. MTHFR and apo E affect blood lipid levels, which was statistically confirmed. An association was also recorded between hyperhomocysteinemia and patients with CS. Vitamin status in CS showed a statistically verified association with TC/TT MTHFR genotype. In the group of patients with TC/TT MTHFR genotype, lower vitamin B12 and higher folate values were recorded. The results of multiple logistic analysis showed that there was no statistical significance of Hcy levels (OR 2.403, p=0.334) or conventional vascular risk factors such as smoking habit (OR 0.505, p=0.149), age (OR 1.048, p=0.087) or sex (OR 2.037, p=0.112) in predicting CS.     

Polymorphism of the apolipoprotein E gene (APOE) in the populations of Russia and neighboring countries

Allele and genotype frequencies for the locus encoding apolipoprotein E, involved in the regulation of lipid metabolism (APOE), were evaluated in 16 populations representing 12 ethnic groups (a total of 1103 subjects) from Russia and neighboring countries. In the populations examined, the frequencies of allele epsilon4, which is the risk factor of Alzheimer's disease and coronary heart disease, varied from less than 5 to more than 20%, while the variation of the major epsilon3 allele in these populations ranged from less than 75 to 95%. The frequencies of alleles epsilon3 and epsilon4 were 0.714 and 0.205 in Saami, 0.734 and 0.149 in Maris, 0.841 and 0.122 in Evenks, 0.788 and 0.163 in Buryats, 0.764 and 0.202 in Chukchi, 0.875 and 0.075 in Iranians, 0.956 and 0.044 in mountain-dwellers of the Pamirs, 0.771 and 0.094 in Ukrainians, and 0.795 and 0.091 in Belarussians, respectively. In Russians from different regions of the country, the frequencies of these alleles were 0.728 and 0.139 (Kostroma), 0.795 and 0.105 (Moscow), 0.857 and 0.092 (Rostov-on-Don), and 0.824 and 0.083 (Krasnodar), respectively. The latitudinal distribution of the APOE epsilon3 and epsilon4 allele frequencies in the populations examined was comparable to the frequency distribution pattern of these alleles in other populations of Eurasia.     

Is the ApoE polymorphism associated with dilated cardiomyopathy?

Apolipoprotein E (ApoE) is 34 kDa protein involved in the modulation of cholesterol transport and homeostasis. Polymorphism of the ApoE gene has been implicated in many chronic cardiovascular and neuronal diseases. ApoE epsilon4 allele has been reported to be associated with increased risk of cardiovascular diseases such as myocardial infarction, hypertension, coronary heart disease, etc. Fifty patients with the end-stage dilated cardiomyopathy (DCM) and advanced congestive heart failure were examined in our study. For evaluation of ApoE polymorphism, novel approach of fast screening of ApoE gene polymorphism by combination of PCR and blotting (CVD StripAssay) was used. Individual genotypes were correlated with basic cardiologic clinical parameters. The reported frequency of this allele in Caucasian population is 14.7 %. Our results showed that in patients with DCM frequency of the ApoE epsilon4 allele is 40 %. Frequency of the genotype epsilon2/4 was 58 % and epsilon3/4 was 22 %. Comparison with control Caucasian groups monitored by others clearly revealed that frequency of epsilon4 alelle is increased in patients with advanced stages of DCM. This observation suggests association of ApoE polymorphism with severe form of DCM. Physiological consequences of this observation remain to be clarified.     

Modulation of plasma triglyceride levels by apoE phenotype: a meta-analysis.

The relationship between apoE phenotype and plasma lipid levels was analyzed in the combined data of published studies. Accordingly, 45 population samples from 17 different countries were included in the analysis. The mean plasma values of cholesterol (CH), triglyceride (TG), and high density lipoprotein (HDL)-CH of the apoE 2/2, 3/2, 4/3, 4/4, and 4/2 groups were compared with the same parameters of the E 3/3 subset. The standardized difference between the plasma lipid concentrations of the apoE subgroups and of their respective apoE 3/3 control (Z-score), as well as their mean weighted value, were calculated for each study and in each subgroup. The analysis confirmed that subjects carrying the epsilon 2 and epsilon 4 alleles had, respectively, lower (Z2/2 = -0.39, Z3/2 = -0.34) and higher (Z4/3 = 0.15, Z4/4 = 0.29) plasma cholesterol values than subjects carrying the epsilon 3/epsilon 3 genotype. In addition, results indicated a consistent relationship between plasma TG levels and apoE phenotype among different populations. TG concentrations were significantly higher in apoE 2/2, 3/2, 4/3 and E 4/2 than in E 3/3 subsets (Z2/2 = 0.42, Z3/2 = 0.14, Z4/3 = 0.13, Z4/2 = 0.19). Further, this trend was found in samples of normolipidemic adults and children, in diabetic and obese individuals, as well as in hyperlipidemic subjects indicating an ubiquitous relationship. Concurrently, HDL-CH was significantly lower in the apoE 4/3 (Z4/3 = -0.09) than in the E 3/3 subset.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evidence that the apolipoprotein E-genotype effects on lipid levels can change with age in males: a longitudinal analysis.

We previously reported that change, with age, in plasma levels of total cholesterol (TC) and LDL cholesterol (LDL-C) differed between apolipoprotein E (APOE) genotypes epsilon 3 epsilon 3 and epsilon 3 epsilon 4, in a sample of 77 older, unrelated males. By use of a larger sample from that cohort, followed longitudinally during 1969-87, the change in TC and in LDL-C, between the epsilon 3 epsilon 3 and epsilon 3 epsilon 4 APOE genotypes, over three exams, was reanalyzed. Additionally, the change in triglycerides (TG) and in HDL-cholesterol (HDL-C), between the epsilon 3 epsilon 3 and epsilon 3 epsilon 4 APOE genotypes-as well as the differences between the epsilon 3 epsilon 3 and epsilon 3 epsilon 2 genotypes, for TC, LDL-C, TG, and HDL-C-were contrasted over the three exams. At exam 1 TG was higher in the epsilon 3 epsilon 4 group than in the epsilon 3 epsilon 3 group (mean age 48 years), and at exams 2 and exam 3 (mean ages 58 and 63 years, respectively) it was similar (P = .009 for the exam-by-genotype-interaction effect in the repeated-measures analysis). A similar trend was seen for TC (P = .03), yet previously detected LDL-C effects were not apparent (P = .46). Those with the epsilon 3 epsilon 2 genotype had higher TG and lower LDL-C and TC at each exam than were seen in those with the epsilon 3 epsilon 3 genotype, although the differences in the values were not always statistically significant. Differences in TC, LDL-C, and TG, between the epsilon 3 epsilon 2-genotype and epsilon 3 epsilon 3-genotype groups, did not significantly change over the three exams. HDL-C levels were relatively stable over the exams; however, the exam-by-genotype interaction was significant for the epsilon 3 epsilon 2 genotype versus the epsilon 3 epsilon 3 genotype (P = .02). The epsilon 4 allele effects on TG and TC changed between longitudinal exams and may be age dependent. Changes, with age, in the effect of the epsilon 3 epsilon 4 genotype on lipids may impact the risk of developing atherosclerotic disease.     

Coenzyme Q10, antioxidant status and ApoE isoforms

The aim of this study was to inquire the antioxidant status in plasma and lipoproteins isolated from normal subjects possessing different ApoE genotypes. For this purpose we investigated blood samples from 106 healthy blood donors: the distribution of ApoE alleles (E2/E2 = 0.9%, E2/E3 = 10.4%, E2/E4 = 2.8%, E3/E3 = 71.7%, E3/E4 = 12.3% and E4/E4 1.9% with 1, 11, 3, 76, 13, and 2 subjects respectively for each genotype) was in agreement with previous data. Almost no differences were found in the concentrations of both coenzyme Q10 (CoQ10) and vitamin E for the different genotypes. Concentration of CoQ10 in isolated lipoproteins was also similar, in the different genotypes, when referred to cholesterol; CoQ10 in LDL was higher for the E3/E3 subjects when referred to protein. Neither CoQ10 nor vitamin E correlated with paraoxonase (PON) activity or cholesteryl-ester hydroperoxides (CHP). Furthermore, there was no correlation between the same lipophilic antioxidants and CHP levels. The only E2 homozygous subject found had high levels of PON and low levels of CHP; the two E4/E4 subjects had low PON activity together with low levels of CHP.     

Impact of Apo E gene polymorphism on HCV therapy related outcome in a cohort of HCV Egyptian patients

The functional apolipoprotein E (Apo E) gene polymorphism could be used as a determinant of outcome of HCV infection. This study aimed to demonstrate the impact of Apo E genotype on the response to HCV combined therapy. Material and methods: The study has been implemented on 125 individuals with persistent HCV infection and 120 cases with sustained virologic response (SVR). All participants were genotyped for ApoE gene polymorphism by a real-time quantitative PCR (qPCR). Results: Statistically significant differences were demonstrated regarding the Apo E genotypes between the two groups (P-value?<?.001) where the frequency of E3E3 was significantly higher among the chronic HCV-patients while E3E4 and E4E4 genotypes frequencies were higher among the SVR-subjects group and E3E3 genotype was associated with increased risk of chronicity (OR 4.7; 95% CI 1.9–12.1, P-value?<?.001). Moreover, There were statically significant differences regarding E3 and E4 alleles frequencies, where E3 allele display a higher frequency among the chronic HCV-patient group while the SVR-subjects group showed higher frequency of E4 allele and the carriers of E3 allele have 1.4 times more risk to develop chronicity than those with E4 allele (OR 1.4; 95% CI 1.0–2.0, P-value?<?.05). Meanwhile the protective E2 allele was absent in all infected participants. Conclusion: This study supports the hypothesis of the protective impact of Apo E4 allele that favors viral clearance of HCV infection and its recovery after combined therapy, while the Apo E3 allele is considered as a particular risk factor for the chronicity in HCV patients and resistance to therapy. Whereas the Apo E2 allele confers a resistance to HCV infection at a time of exposure.     

Genotypes of vitamin-D-binding protein (DBP) in patients with chronic obstructive pulmonary disease and healthy population of Republic Bashkortostan

The distribution of alleles and genotypes of vitamin D-binding protein (DBP) gene has been studied in patients with Chronic Obstructive Pulmonary Disease (COPD, n = 298) and healthy individuals (n = 237) from two ethnic groups (Tatars and Russians) living in Republic Bashkortostan. Statistically significant differences in the distribution of DBP gene genotypes between Tatars and Russians (chi2 = 8.854, df = 5, P = 0.04) were revealed. The pattern of allele's distribution within DBP gene was similar in healthy control subjects of both ethnic groups, with gradient reduction in row GC*1S> GC*1F> GC*2. The most common genotypes were: GC*1F/1S in Tatars (36.79%) and GC*1S/2 in Russians (34.62%). It has been shown, that Tatars with genotype GC*1F/1S have a lower risk of COPD development: the frequency of GC*1F/1S genotype in COPD patients was significantly lower than in healthy individuals (19.85% versus 36.79%; chi2 = 7.622, P = 0.0067, Pcor = 0.0335; OR = 0.42 CI 95% 0.22-0.79). At the same time, COPD patients from the same group had higher frequency of GC* 1F/2 genotype than healthy individuals (19.08% versus 8.49%; chi2 = 4.52, P = 0.033, Pcor = 0.165; OR = 2.54 CI 95% 1.067-6.20). In Russian population the distribution of alleles and genotypes of DBP gene were similar in COPD patients and healthy individuals.     

ApoE genotype affects allele-specific apo[a] levels for large apo[a] sizes in African Americans: the Harlem-Basset Study

The genetic variability of apolipoprotein E (apoE) influences plasma lipoprotein levels, and allele frequencies differ between African Americans and Caucasians. As African Americans have higher lipoprotein [a] (Lp[a]) levels than Caucasians, we investigated the effects of the apoE gene on allele-specific apolipoprotein [a] (apo[a]) levels across ethnicity. We determined apo[a] sizes, allele-specific apo[a] levels (i.e., levels associated with alleles defined by size), and the apoE gene polymorphism in 231 African Americans and 336 Caucasians. African Americans, but not Caucasians, with the apo E2 genotype had lower levels of Lp[a] compared with those with the apo E4 genotype (9.6 vs. 11.2 nmol/l; P = 0.034, expressed as square root levels). Distribution of apo[a] alleles across apoE genotypes were similar between African Americans and Caucasians. Among African Americans with large apo[a], the allele-specific apo[a] level was significantly lower among epsilon2 carriers compared with epsilon3 or epsilon4 carriers (5.4 vs. 6.6 and 7.4 nmol/l, respectively; P < 0.005, expressed as square root levels). In contrast, there was no significant difference in allele-specific apo[a] levels across apoE genotypes among Caucasians. For large apo[a] sizes, apoE genotype contributed to the observed African American-Caucasian differences in allele-specific apo[a] levels.     

Oxidative damage and protection by antioxidants in the frontal cortex of Alzheimer's disease is related to the apolipoprotein E genotype.

A great number of epidemiological studies have demonstrated that the frequency of the epsilon4 allele of the apolipoprotein E gene (APOE) is markedly higher in sporadic and in familial late onset Alzheimer disease (AD). In the frontal cortex of AD patients, oxidative damage is elevated. We address the hypothesis that the APOE genotype and reactive oxygen-mediated damage are linked in the frontal cortex of AD patients. We have related the APOE genotype to the levels of lipid oxidation (LPO) and to the antioxidant status, in frontal cortex tissues from age-matched control and AD cases with different APOE genotypes. LPO levels were significantly elevated in tissues from Alzheimer's cases which are homozygous for the epsilon4 allele of APOE, compared to AD epsilon3/epsilon3 cases and controls. Activities of enzymatic antioxidants, such as catalase and glutathione peroxidase (GSH-PX), were also higher in AD cases with at least one epsilon4 allele of APOE, while superoxide dismutase (SOD) activity was unchanged. In the frontal cortex, the concentration of apoE protein was not different between controls and AD cases, and was genotype independent. The Ginkgo biloba extract (EGb 761), the neurosteroid dehydroepiandrosterone (DHEA) and human recombinant apoE3 (hapoE3rec) were able to protect control, AD epsilon3/epsilon3 and epsilon3/epsilon4 cases against hydrogen peroxide/iron-induced LPO, while hapoE4rec was completely ineffective. Moreover, EGb 761 and DHEA had no effect in homozygous epsilon4 cases. These results demonstrate that oxidative stress-induced injury and protection by antioxidants in the frontal cortex of AD cases are related to the APOE genotype.