APOE Allele Frequencies Research Articles

Exploratory Study of Apolipoprotein E ε4 Genotype and Risk of Alzheimer's Disease in Mexican Hispanics

To the Editor: Hispanics are 1.5 times more likely to develop Alzheimer's disease (AD) than White non-Hispanics1. A community-based study reported that the prevalence of AD is higher in Hispanics than in White non-Hispanics2. Interestingly, a recent study found that the average proportion of Amerindian genetic ancestry in AD cases was a third of that observed in the cognitively intact controls3. These findings suggest that Amerindian ancestry confers a protective effect against disease onset. Hispanics are a mixture of European, African, and Amerindian genomes, with percentages depending on the country of origin4. Individuals of Mexican origin generally are of Amerindian ancestry, while those of Caribbean origin, for example, have more African ancestry5,6. Therefore, the question arises as to whether Mexican Hispanics differ in their susceptibility to AD. The Apolipoprotein E (APOE) gene, with its three common alleles (e2, e3, e4), is involved in cholesterol transport and other biologic pathways potentially relevant to AD7 and has been consistently associated with an increased risk of AD8. Studies indicate that the APOE genetic risk variants may not carry the same risk for Hispanics as for White non-Hispanics. A meta-analysis found an association between the APOE-e4 allele and AD, although the risk conveyed by the APOE-e4 allele frequency was found to be lower in Hispanics, predominately Caribbean origin, than in White non-Hispanics9. Another study of Hispanic Americans of predominantly Caribbean origin showed a smaller relative risk of AD conveyed by the APOE-e4 allele in Hispanics than in White non-Hispanics10. To our knowledge, Mexican Hispanics have not been studied as a single group to determine the associated risk between the APOE-e4 allele and AD onset.

Relationship of apolipoprotein E polymorphism with lipid profiles in atherosclerotic coronary artery disease

Aims: The aim was to determine the relationship between apolipoprotein E (ApoE) gene polymorphisms and lipid profile in patients with coronary artery diseases (CAD), and its role in the prediction of the severity of carotid and coronary atherosclerosis. Methods and results: One hundred patients were classified by coronary angiography: 80 patients with CAD and 20 controls (normal coronary angiography). Clinical data, carotid sonography, blood lipid profiles and ApoE genotyping (PCR-RFLP) were assessed. CAD patients had significantly increased plasma lipid profiles and carotid intimal-wall thickness (IMT) versus controls. In CAD patients; ApoE genotype frequencies were E3/E3 = 62.50%, E2/E3 = 18.75%, E3/E4 = 17.50%, E2/E4 = 1.25%, E4/E4 = 0 and E2/E2 = 0. But, E3/E4 genotype was significantly higher than con- trols (P < 0.05). Also, in CAD patients; ApoE allele frequencies were E3 = 80.6%, E2 = 10.0% and E4 = 9.4% but, ApoE4 alleles were associated with higher cholesterol (P = 0.034) and LDL- c( P = 0.003), while ApoE2 alleles were associated with higher triglycerides (P = 0.037) versus ApoE3 alleles. However, odds ratio of CAD patients had higher risk with E2/E3 genotypes (2.5- fold), E2 alleles (2.2-fold) and E4 alleles (2.1-fold). Moreover, CAD patients with ApoE4 alleles had significantly higher carotid IMT (1.23 ± 0.26 mm vs 0.97 ± 0.2 mm ApoE3, P = 0.006; how- ever, non-significant vs 1.10 ± 0.40 mm ApoE2 and also, ApoE2 vs ApoE3 alleles, P = 0.633) and left anterior descending (LAD) coronary artery stenosis (vs ApoE3 alleles, P = 0.016). Conclusion: Ischemic patients with carotid and coronary atherosclerosis had significantly higher integration of dyslipidemia and ApoE alleles (ApoE2 with hypertriglyceridemia and ApoE4 with hypercholesterolemia and higher LDL-c). ApoE polymorphism may be an important diagnostic risk biomarker and may implicate therapeutic intervention in atherosclerotic ischemic patients.

Characterization of Mexican Americans with mild cognitive impairment and Alzheimer's disease.

The purpose of the study was to provide characterization of Mexican Americans who meet criteria for Alzheimer's disease (AD) and mild cognitive impairment (MCI). For the study, 1,069 participants ages 40 and above who self-identified as either non-Hispanic white (n = 633) or Mexican American (n = 436) were recruited using a community-based participatory research approach. Global cognition was assessed via the Mini-Mental State Examination (MMSE), dementia severity by the Clinical Dementia Rating Scale, and depression via the Geriatric Depression Scale 30-item version. Age, gender, education, ApoE ε4 allele frequency, and diabetic diagnoses were also analyzed. The findings showed that Mexican Americans (normal controls, MCI, and AD) were younger, less highly educated, performed more poorly on the MMSE, endorsed more symptoms of depression, were more likely to be diagnosed with diabetes, and possessed the ApoE ε4 allele less frequently. Age was the only significant risk factor for cognitive dysfunction (AD/MCI) among Mexican Americans (OR = 1.06, 95% CI = 1.03-1.09). Age (B = 0.07, std = 0.02, p < 0.001) and ApoE ε4 presence (B = 0.9, std = 0.4, p = 0.02) were significantly related to increased disease severity. Given the rapidly growing and aging Mexican American population, there is a substantial need for research into cognitive aging, MCI, and AD among this ethnic group. The current findings hold important implications for both clinic and research settings and point to additional research needs.

Homozygosity for the APOE E4 Allele is Solely Associated with Lower Cognitive Performance in Brazilian Community-dwelling Older Adults – The Bambuí Study

To investigate if APOE E4 allelic status is associated with the cognitive functioning of elderly individuals. Participants (n = 1,408) from the Bambuí Cohort Study of Aging were selected based on the results from both variables (APOE genotype and MMSE score). Gender, age, education, marital status, skin color, GHQ score and biological measures were used as confounding factors for adjusting the logistic regression. The population was in Hardy-Weinberg equilibrium, and the APOE E4 allele frequency was 13.4%. APOE E4 allele homozygosity conferred a superior odds ratio (OR) for cognitive impairment (OR = 3.1) compared to E4 allele heterozygosity (OR = 0.99) even when adjusted for age, sex, education, marital status, skin color, triglycerides, HDL, systolic pressure, and GHQ (OR = 2.9). No differences were observed between the other covariates. The APOE E4 allele was observed to have a dramatic effect on cognitive impairment, especially in homozygotes, which comprised approximately 2% of the population.

Alzheimer’s disease and type 2 diabetes: the association study of polymorphisms in tumor necrosis factor-alpha and apolipoprotein E genes

Type 2 diabetes (T2D) and Alzheimer's disease (AD) are two progressive disorders with high prevalence worldwide. Polymorphisms in tumor necrosis factor-alpha (TNF-α) and apolipoprotein E (ApoE) genes might be associated with both T2D and AD, representing possible genetic markers for the development of the AD in subjects with T2D. The aim was to determine ApoE and G-308A TNF-α gene polymorphisms in unrelated Croatian Caucasians: 207 patients with sporadic AD, 196 T2D patients and 456 healthy controls. Patients with AD had higher frequency of ApoE4 allele compared to T2D patients and controls. The significant association, observed between ApoE2 allele and T2D, disappeared after the data were adjusted for age and sex. The genotype or allele frequencies of G-308A TNF-α gene polymorphism were similar among the patients with AD, T2D and healthy controls. In conclusion, these results do not support the hypothesis that the A allele of G-308A TNF-α gene polymorphism is associated either with AD or T2D. Our data confirm the association between the ApoE4 allele and AD, and point out the E2 allele of ApoE gene as the possible risk factor for T2D.

ApoE4 and late onset depression in Indian population

ApoE4 is a 'risk factor' for cognitive disorders like Alzheimer's dementia, and Late Onset Depression (LOD) is a forerunner of dementia. There is thus a need to study the association between ApoE4 allele and LOD. The study assessed the frequency of ApoE4 allele in 31 cases of LOD above the age of 50 years and 31 matched controls. The subjects were assessed on various clinical parameters towards diagnosis. There was a significant association between the ApoE4 allele and LOD in comparison to controls (Odd's ratio=4.7, Confidence Interval=1.12 to 19.79, P=0.035). ApoE4 allele had no association with the age of onset of depression, cognitive functions and severity of LOD. Individuals with LOD have a significantly higher frequency of the ApoE4 allele. In other words, elderly in India with an ApoE4 allele have 4.7 times more risk of developing depression in old age. Within LOD group there is no difference between those with and without ApoE4 accordingly in age of onset of depression, cognitive functions and severity of LOD.

The Relationship of Cardiovascular Risk Factors to Alzheimer Disease in Choctaw Indians

To test the hypothesis that cardiovascular risk factors (CRFs) influence predisposition to and the clinical course of Alzheimer disease (AD), the authors compared Choctaw Indians, a group with known high CRF with white persons with AD. In addition to CRF history, the authors investigated the frequency of apolipoprotein E4 (apoE4) genotype andplasma homocysteine (HC) levels. The authors compared 39 Choctaw Indians with AD and 39 Choctaw Indians without AD to 39 white persons with AD with all groups similar in age. CRF history included diabetes, hypertension, high cholesterol or hypolipidemic agent use, or myocardial infarction. The authors also compared plasma HC concentration and apoE4 allele frequency. Choctaw persons with AD differed significantly from white persons with AD in history of hypertension, diabetes, and in HC values but not from Indians without AD. There was a significantly lower apoE4 allele frequency in Choctaw Indian AD than white persons with AD, and both AD groups had an affected first degree relative significantly more often than Indian controls. There was no relationship between the number of CRF and age at onset among Indians or whites, whereas HC concentration was associated with significantly earlier age of onset for Choctaw Indians but not for whites. This small study suggests that in Choctaw Indians modifiable risk factors may play more of a role in disease pathogenesis than in whites and that nonmodifiable risk factors such as apoE4 may play less of a role.

Cholesterol ester transfer protein and apolipoprotein E gene polymorphisms in hyperlipidemic Asian Indians in North India

We determined the distribution of the polymorphic variants of CETP TaqIB and ApoE genes and their association with lipid and anthropometric parameters in hyperlipidemic and normolipidemic Asian Indians in North India. CETP TaqIB and ApoE polymorphism were assayed by PCR-RFLP in hyperlipidemic (n = 220) and normolipidemic (n = 367) subjects. Plasma lipids levels were estimated using commercially available kits from Randox (USA). The distribution of CETP TaqIB genotypes and alleles did not differ between the two groups. The frequency of ApoE ε4 allele was significantly higher in hyperlipidemic than normolipidemic subjects. Serum lipid levels were comparable between subjects with the different CETP TaqIB and ApoE genotypes in the two groups. Multivariate analysis after adjusting for age, sex, BMI, WHR, and total skinfold thickness showed that subjects with the Ε3Ε4 genotype and ε4 allele carriers were at significantly higher odds to develop hyperlipidemia [2.07 (1.29-3.30) and 2.05 (1.30-3.24), respectively] as compared to the other genotypes. ApoE ε4 allele and E3E4 genotype emerged as important genetic markers for hyperlipidemia in this study population.

Relationship between ApoE gene polymorphism and coronary heart disease in Gaza Strip

Background:Apolipoprotein E (ApoE) plays a role in the regulation of lipid metabolism in humans. ApoE, a 229-amino-acid polypeptide, is classified into three major isoforms (E2, E3, and E4) according to the differences in amino acids at positions 112 and 158. In the normal population, ApoE3 isoform is the most prevalent, and ApoE2 or E4 is frequently associated with hyperlipoproteinemia. The objective of this work was to investigate the relationship between ApoE gene polymorphism and coronary heart disease (CHD) in Gaza Strip and investigate the association between serum lipid levels and CHD.Material and Methods:The study population consisted of 137 subjects including 69 CHD cases (45 male, 24 female) and 68 healthy subjects (33 male and 35 female).Results:The ApoE3/E3 genotype was the most common in the control and the CHD groups. ApoE2/E3 and ApoE3/E4 were the next most common genotypes. The frequencies of ApoE alleles in the CHD subjects were 0.826 for E3, 0.137 for E4, and 0.0362 for E2. These frequencies are comparable to those found in the control group which were 0.875 for the E3, 0.073 for E4, and 0.0515 for E2. No statistically significant differences in ApoE genotypes were found between the patients and the control groups. Moreover, there was no significant difference between the mean of triglyceride (TG) and HDL levels among different ApoE genotypes. However, there was a significant difference in the mean of LDL and ApoE genotypes where the mean of LDL was 218.17 mg/dl in ApoE4, 149.67 mg/dl in ApoE2, and 184.52 mg/dl in ApoE3. A significant difference was also evident between the mean of LDL levels in the CHD and the control group where the mean of LDL was 126 mg/dl in CHD and 111.47 mg/dl in the control group. Our study indicated that there was no significant difference between the mean of cholesterol and TG levels of the CHD and the control groups.Conclusions:To our knowledge, this is the first study in Gaza Strip investigating the relation between ApoE genotypes and CHD. Further investigations are needed to link other genetic factors to CHD.

The roles of ultraviolet-B irradiance, vitamin D, apolipoprotein E ε4, and diet in the risk of prostate cancer

There have been a number of papers investigating the riskmodifying factors for prostate cancer, with diet, ultraviolet-B (UVB), and genetics among the leading factors considered, but there is still no agreement on the relative contribution of these factors. For example, the paper by Barnett et al. [1] found no link in their recent study between prediagnostic serum 25-hydroxyvitamin D [25(OH)D] and prostate cancer incidence in older men during a mean 5.3-year followup period [1]. This finding agrees with those of other recent reviews [2–4]. However, studies looking at prostate cancer incidence with respect to personal UVB irradiance ([5] and Refs. 31–33 in [1]) offer some of the more convincing evidence for a role of UVB and vitamin D in reducing the risk of prostate cancer. These studies were based on earlylife and/or long-term UVB irradiance, and prostate cancer is a type of cancer that progresses very slowly. There is also good evidence that vitamin D improves survival for those diagnosed with prostate cancer (Refs. 34 and 35 in [1]). Thus, vitamin D appears to be important in reducing the risk of prostate cancer over many years, so measuring 25(OH)D levels shortly before diagnosis of prostate cancer may not provide an accurate indication of the overall effect of vitamin D on prostate cancer risk. Although ecological studies have reported inverse correlations between solar UVB and prostate cancer incidence and/or mortality rates (Refs. 2, 28–30 in [1]), UVB may not be the only factor affecting the geographic variations. An inspection of the prostate cancer mortality rate maps in the Atlas of Cancer Mortality Rates in the United States, 1950– 1994 [6] indicates that the mortality rates are dissimilar from those of well-known vitamin D–sensitive cancers such as breast and colorectal cancer [4]. The highest rates for prostate cancer are in the northwest and the lowest are in the southeast, whereas the highest rates for breast and colorectal cancer are in the northeast and the lowest are in the southwest. Analysis of the map of greatest ancestry by county in the United States [7] found high correlations for many of the high-resolution features in prostate cancer and ancestry maps. This finding suggested that ethnic background played an important role in prostate cancer risk, which could be due to a combination of dietary and genetic factors. This finding formed the basis for a multicountry ecological study in which the apolipoprotein E e4 (ApoE4) allele and per capita gross domestic product correlated directly with prostate cancer incidence and mortality rates, and fraction of energy derived from cereals/grains correlated inversely [8]. Although this result is currently a hypothesis, it also explains several findings of prostate cancer epidemiology. It explains why black Americans, with nearly twice the ApoE4 allele prevalence of white Americans, have about twice the rate of prostate cancer [6]. It supports the finding that cholesterol is often a risk factor for prostate cancer but not for any other cancer [9]. It explains why those who develop type 2 diabetes mellitus have a reduced risk for prostate cancer [10]: the ApoE2 allele is an important risk factor for type 2 diabetes mellitus [11], and those who have ApoE2 have a reduced prevalence of ApoE4 [12]. Trying to evaluate the ApoE4 hypothesis, perhaps by looking at frequencies of various ApoE alleles of those diagnosed with prostate cancer, seems worthwhile. The literature contains one paper [13] that supports this W. B. Grant (&) Sunlight, Nutrition, and Health Research Center (SUNARC), P.O. Box 641603, San Francisco, CA 94164-1603, USA e-mail: wbgrant@infionline.net URL: www.sunarc.org

Characteristics of Dyshoric Capillary Cerebral Amyloid Angiopathy

Cerebral amyloid angiopathy (CAA) affects brain parenchymal and leptomeningeal arteries and arterioles but sometimes involves capillaries (capCAA) with spread of the amyloid into the surrounding neuropil, that is, dyshoric changes. We determined the relationship between capCAA and larger vessel CAA, β amyloid (Aβ) plaques, neurofibrillary changes, inflammation, and apolipoprotein E (APOE) in 22 cases of dyshoric capCAA using immunohistochemistry. The dyshoric changes contained predominantly Aβ1-40, whereas dense bulblike deposits adjacent to the capillary wall contained mostly Aβ1-42. There was an inverse local correlation between Aβ plaque load and capCAA severity (p = 0.01), suggesting that Aβ transport between the neuropil and the circulation may be mechanistically involved. Deposits of hyperphosphorylated tau and ubiquitin and clusters of activated microglia, resembling the changes around Aβ plaques, were found around capCAA but were absent around larger vessel CAA. In 14 cases for which APOE genotype was available, there was a high APOE-ε4 allele frequency (54%; 43% homozygous). The severity of CapCAA increased with the number of ε4-alleles; and APOE4 seemed to colocalize with capCAA by immunohistochemistry. These results suggest that capCAA is pathologically and possibly pathogenetically distinct from larger vessel CAA, and that it is associated with a high APOE-ε4 allele frequency.

Tarot decks and PET scans

Although there have been meaningful advances in our understanding of the symptoms and underlying pathogenesis of Alzheimer disease (AD), we still cannot predict which individuals with mild cognitive impairment (MCI) will worsen or develop AD. There is a pressing need for identification of optimal clinical biomarkers to predict progression and conversion to dementia in patients with MCI. This important issue is tackled in the current issue of Neurology ®. Landau et al.1 compared genetic ( APOE e4 allele frequency), biochemical (CSF Aβ1–42, t-tau, p-tau181p), functional and structural neuroimaging (FDG-PET, hippocampal volume), and cognitive (episodic memory performance) biomarkers in a large group of patients with MCI to determine which combination had the best predictive value for progression or conversion to AD. Their major finding was that patients with amnestic MCI with abnormal FDG-PET and low episodic memory performances were almost 12 times more likely to convert to AD than individuals who were normal on both measures. CSF markers and, marginally, FDG-PET abnormalities were predictors of cognitive decline. Landau et al. concluded that …

Association between apolipoprotein ε4 allele, factor V Leiden, and plasma lipid and lipoprotein levels with sickle cell disease in southern Iran

To investigate whether there is any association between various APOE alleles and factor V Leiden (FVL) with lipid profiles and sickle cell disease (SCD) in Southern Iran. 65 SCD patients consisting of 35 sickle cell anemia homozygous (SS), 15 sickle cell heterozygous (AS) and 15 sickle cell/βThalassemia (S/βthal) patients and 68 healthy individuals with normal hematological indices were studied. APOE and FVL polymorphisms were detected by PCR-RFLP and serum lipid level was measured enzymatically. The frequencies of FVL and APOE-ε4 allele were significantly higher in SCD patients than in control (15.4 vs. 4.4 and 13.7% vs. 3.3%, respectively). The distributions of APOE ε3ε3, ε2ε3 and ε2ε4+ε3ε4 alleles in SCD patients were significantly different from those in the control group. The SCD subjects particularly SS/S βthal (SS+S/βthal) and SS patients have significantly lower frequency of APOE ε3ε3 allele (P<0.05) whereas SCD, SS patients and AS individuals have a significantly higher frequency of APOE ε4 allele (ε2ε4+ε3ε4; P=0.003, P=0.011 and P=0.035, respectively) compared to the control group. The LDL-C (P=0.006) and total cholesterol (P<0.001) levels in SCD subjects were found to be significantly lower than those in the control group. In addition, the presence of non-APOE ε4 allele (ε2ε3+ε3ε3) resulted in a significant decrease in the level of LDL-C and total cholesterol in SCD subjects in general and in SS and SS/S βthal patients in particular compared to controls. Furthermore, the presence of APOE ε4 allele (ε2ε4+ε3ε4) was found to be associated with the risk of sickle cell anemia [OR=4.1, P=0.04]. The presence of either FVL mutation (OR=4.6; CI: 0.91-24, P=0.07) or APOE-ε4 allele (OR=4.07; CI: 1.01-16.4, P=0.048) is associated with the risk of sickle cell disease in Southern Iran. This data suggest that the activation of coagulation system enhances thrombus generation and decreases antioxidant activity in SCD patients from Southern Iran.

Does the geographical gradient of ApoE4 allele exist in China? A systemic comparison among multiple Chinese populations

The allelic frequencies of apolipoprotein E (apoE) vary substantially around the world. There is a conspicuous south-to-north gradient of e4 frequencies in Europe, with the proportion of e4 carriers from only 10-15% in the south to 40-50% in the north. The mechanism may be related to the possibility that e4 carriers are less likely to develop vitamin D deficiency. In addition, Asian populations traditionally have lower e4 frequency than Europeans, which may be attributed in part to the scarce or irregular food supplies in Western world in the recent past. However, whether these geographical distribution gradients exist in China is yet unknown. ApoE genotypes of 200 children from Nanning City were determined by PCR-restriction fragment length polymorphism (RFLP) analysis. Allele frequency data of 18 other populations were collected from published sources and correlated with latitude and longitude information from different geographic resources. In our subjects, the frequencies of apoE genotypes were E3/E3: 73.0%, E3/E2: 15.0%, E4/E3: 5.0%, E4/E4: 5.0%, and E4/E2: 2.0%; the frequencies of apoE alleles were e2: 8.5%, e3: 83.0%, and e4: 8.5%, respectively. The total sample consisted of 3,679 individuals from 19 Chinese populations; the allelic frequencies were e2: 7.6%, e3: 85.5%, and e4: 6.9%, respectively; the proportion of e4 carriers was from 4.9% in Kunming to 17.5% in Harbin. Systemic comparison among multiple Chinese populations revealed that positive correlation existed between the e4 allele frequency distribution and latitude north (r=0.586, P=0.008), but no correlation of the e4 allele frequency distribution with longitude east was found (r=-0.018, P=0.942). We conclude that there is a south-to-north, but not an east-to-west gradient for the apoE4 allele in China.

Comparative study of apolipoprotein-E polymorphism and plasma lipid levels in dyslipidemic and asymptomatic subjects, and their implication in cardio/cerebro-vascular disorders

Polymorphisms in the apolipoprotein-E (apoE) gene may modulate lipoprotein metabolism at different steps and influence total and low density lipoprotein (LDL) cholesterol (LDLc) levels, as well as other lipid features. Population studies have documented significant differences in the frequency of apoE alleles which are related to the prevalence of various cardio-vascular and neuro-psychiatric diseases. In this study, the apoE genotypes and allele frequencies were analyzed in 216 individuals (109 dyslipidemic and 107 normo-lipidic subjects), and the relative contribution of apoE polymorphism on plasma lipid and lipoprotein levels, as well as risk factors was evaluated. In normo-lipidic volunteers, the frequencies of ɛ2, ɛ3 and ɛ4 alleles were 0.042, 0.832 and 0.126, while in dyslipidemic subjects 0.046, 0.835 and 0.119, respectively. No significant difference was observed among ɛ2, ɛ3 or ɛ4 and plasma lipid-lipoprotein levels in the dyslipidemic group. In normo-lipidemics, however, total cholesterol, LDLc and non-HDLc plasma levels were significantly lower in ɛ2 subjects when compared to ɛ3 and ɛ4 individuals. The allelic frequencies of apoE ɛ2, ɛ3 and ɛ4 were similar in dyslipidemic and normo-lipemic subjects, suggesting that apoE polymorphisms have no effect on plasma lipid-lipoprotein levels in dyslipidemic subjects. In contrast, in normo-lipemic subjects the ɛ2 allele showed to be associated with lower total cholesterol and LDLc levels, the mark of a better lipid profile. Depending on other co-existing factors, the ɛ2 allele, therefore, may play either a protective or pathogenic role. This elementary knowledge is a fundamental prerequisite for a possible diagnostic application of these lipoproteins as biomarkers to predict adverse cardio-vascular and/or neuro-psychiatric maladies.

Diferencias de sexo, edad y lípidos plasmáticos asociadas al polimorfismo de la apolipoproteína E en un grupo de escolares de Quindío, Colombia

Apolipoprotein E (apoE) polymorphism is a genetic determinant of total cholesterol and LDL-c levels. Several studies have examined the relationship between variations at the APO E and cardiovascular disease. It is important to determine this relationship in the Colombian population. The relationship of apoE polymorphisms was associated with lipid profile by age and sex. A sample of 500 children aged 8 to 18 years, were selected from school populations in Quindio Province, Colombia. ApoE genotypes were determined by polymerase chain reaction and restriction enzyme. Lipid profiles were obtained by commercial kits. The apoE allele frequencies were as follows: E3 - 91.6%, E2 - 5.3, and E4 - 3.1%. Genotypic frequencies were as follows: E3/E3 - 90.8%, E2/E3 - 5.6%, and E3/E4 - 3.2%. No homozygotes for E2/E2 and E4/E4 were recovered. Similar genotypic and allelic distribution was found for each gender. ApoE genotype and gender had a significant effect on total serum cholesterol (CT) and low density lipoprotein cholesterol (c-LDL). In boys these variables were related as follows: E4>E3>E2 (p<0.05); in girls the relationships were somewhat changed (E3>E4>E2). High density lipoprotein cholesterol (c-HDL) levels in boys were related as follows: E2>E4>E3; for girls, E4>E2>E3. In boys, for all variables, the protector effect was in E2; but in girls this allele was only a protector for CT and c-LDL, For triacylglycerol (TAG), very low density lipoprotein cholesterol (c-VLDL) and c-HDL, this the protector effect was associated with the E4 allele, (p<0.05). The results suggested that modulation of apoE genotype on plasma lipids was influenced by gender and age, especially in girls older than 10 years.

Role of MAPT mutations and haplotype in frontotemporal lobar degeneration in Northern Finland

BackgroundFrontotemporal lobar degeneration (FTLD) consists of a clinically and neuropathologically heterogeneous group of syndromes affecting the frontal and temporal lobes of the brain. Mutations in microtubule-associated protein tau (MAPT), progranulin (PGRN) and charged multi-vesicular body protein 2B (CHMP2B) are associated with familial forms of the disease. The prevalence of these mutations varies between populations. The H1 haplotype of MAPT has been found to be closely associated with tauopathies and with sporadic FTLD. Our aim was to investigate MAPT mutations and haplotype frequencies in a clinical series of patients with FTLD in Northern Finland.MethodsMAPT exons 1, 2 and 9–13 were sequenced in 59 patients with FTLD, and MAPT haplotypes were analysed in these patients, 122 patients with early onset Alzheimer's disease (eoAD) and 198 healthy controls.ResultsNo pathogenic mutations were found. The H2 allele frequency was 11.0% (P = 0.028) in the FTLD patients, 9.8% (P = 0.029) in the eoAD patients and 5.3% in the controls. The H2 allele was especially clustered in patients with a positive family history (P = 0.011) but did not lower the age at onset of the disease. The ApoE4 allele frequency was significantly increased in the patients with eoAD and in those with FTLD.ConclusionWe conclude that although pathogenic MAPT mutations are rare in Northern Finland, the MAPT H2 allele may be associated with increased risks of FTLD and eoAD in the Finnish population.

Apolipoprotein E Gene Polymorphism and Serum Lipid Levels in the Guangxi Hei Yi Zhuang and Han Populations

Hei Yi Zhuang is an isolated subgroup of the Zhuang minority in China. Little is known about the distribution of apolipoprotein (apo) E genetic variations and its role in lipid metabolism in this population. The present study was undertaken to compare the effect of apoE gene polymorphism on serum lipid levels between the Guangxi Hei Yi Zhuang and Han populations. A total of 873 subjects of Hei Yi Zhuang and 867 participants of Han Chinese were surveyed by a stratified randomized cluster sampling. Genotyping of apoE was performed using polymerase chain reaction and restriction fragment length polymorphism. The frequencies of 2, 3, and 4 alleles were 15.23%, 79.84%, and 4.93% in Hei Yi Zhuang, and 9.23%, 81.43%, and 9.34% in Han (P < 0.001); respectively. The frequencies of 2/ 2, 2/ 3, 2/ 4, 3/ 3, 3/ 4, and 4/ 4 genotypes were 4.70%, 17.86%, 3.21%, 68.16%, 5.50%, and 0.57% in Hei Yi Zhuang, and 2.54%, 9.23%, 4.15%, 70.70%, 12.23%, and 1.15% in Han (P < 0.001); respectively. Total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and apoB levels were lower in Hei Yi Zhuang than in Han (P < 0.01-0.001), but high-density lipoprotein cholesterol (HDL-C) levels and the ratio of apoA-I to apoB were higher in Hei Yi Zhuang than in Han (P < 0.001 for each). There were significant differences in TC, HDL-C, LDL-C, and apoB levels among the six genotypes in both ethnic groups (P < 0.01-0.001). Hyperlipidemia was positively correlated with age, body mass index, hypertension, alcohol consumption, and apoE allele in both populations (P < 0.05-0.001). TC, LDL-C, and apoB levels were positively correlated, and HDL-C levels were negatively associated with apoE genotypes in both ethnic groups (P < 0.001 for all). The differences in the lipid profiles between Hei Yi Zhuang and Han Chinese might partly attribute to the differences in apoE genotypic and allelic frequencies.

Increased frequency of positive family history of dementia in sporadic CJD

Objective To analyze whether a positive family history of dementia (PFHD) is more common in sporadic CJD (sCJD) than in healthy/population controls and to study associated risk factors. Patients/methods Six hundred and eighty-five sCJD patients and 659 sex-/age-matched controls were included. A PFHD in parents/grandparents/siblings was evaluated. The PRNP M129V polymorphism and ApoE genotype in sCJD with/without PFHD were determined by PCR. Results PFHD was found in 12.1% of sCJD patients and 5.6% of controls ( p < 0.001). No significant difference in M129V polymorphism was found between sCJD with and without PFHD. Thirty-six percent of sCJD patients with PFHD, 26% without PFHD and 19% of healthy controls had at least one ApoE4 allele. Compared to controls, ApoE4 allele frequency ( p = 0.005) and proportion of ApoE4 allele carriers ( p = 0.019) were significantly higher in sCJD with PFHD. Interpretation A higher frequency of the ApoE4 allele in sCJD with a PFHD could be indicative of an additional risk factor in CJD.

Apolipoprotein E polymorphism in Southern Iran: E4 allele in the lowest reported amounts

Apolipoprotein E (apoE) with three major alleles E2, E3 and E4 is one of the critical genes in lipid metabolism. Common apoE alleles are in association with an increase in risk for central nervous and cardiovascular diseases such as Alzheimer's disease, dementia, multiple sclerosis, atherosclerosis, coronary heart disease, hyperlipoproteinemia and stroke. ApoE3 is known as the most frequent allele in all populations, while association of apoE gene polymorphism with reported diseases have mostly been related to other two major alleles especially apoE4. To determine of apoE alleles frequencies in Southern Iran and comparison of those frequencies with other populations. DNA was extracted from the whole blood of 198 healthy unrelated candidates from population of Fars Province, Southern Iran, for apoE genotyping who were checked up by a physician. The frequencies of apoE alleles were compared with other populations by chi(2) test. The frequencies of E2, E3 and E4 were 0.063, 0.886 and 0.051 respectively. These values were similar to those reported from populations of Kuwait, Oman, Lebanon, India, Turkey, Greece, Spain, Sardinia Islands of Italy and two Iranian populations but were different from South of Italy and Caucasians in other Europe regions, American, American-Indian, African, East Asian and Saudi populations (P < 0.05). The frequency of E4 allele as a genetic risk factor for some multifactorial diseases in the population of Southern Iran is in the lowest reported amounts in the world. Iranian population has Caucasoid origin but differs from some Caucasian populations in Europe and America. The results of present study are in agreement with the historical evidences which show admixture of Iranian population with other populations and some studies based on genetic polymorphisms in the population of Southern Iran.