Heterogeneity of apolipoprotein E polymorphism in different Mexican populations

Mexico has approximately 100 million inhabitants. Most of the urban Mexican population has been considered mestizo (Indian and Spanish descent), whereas the Indian population predominates in rural areas and small towns in the countryside. In this study we analyzed the apolipoprotein E (APOE) polymorphism in Guadalajara (the second largest metropolitan area of Mexico) and its surrounding areas, two adjoining states (Nayarit and Durango), and an Indian town (Huichol Indians) from western Mexico. APOE*3 was the most common allele, and APOE*3/*3 was the most common genotype in all populations studied. Guadalajara revealed the highest frequency of the APOE*2 allele (7.8%); the frequency decreased in the rural area (4.4%), followed by Nayarit (1.6%), and was absent in Durango and in the Huichols. On the contrary, the lowest frequency of the APOE*4 allele was in Guadalajara (8.4%); the frequency increased in the rural area (9.3%), in Nayarit and Durango (11.5% and 11.7%), and reached a high frequency in the Huichol Indians (28%). The distribution of the APOE allele in the western population of Mexico is similar to those described in Mexican American migrants living in the United States but is different from those populations living in Mexico City. This study shows the heterogeneity of the Mexican population, where the frequency of the APOE*2 allele is higher in Guadalajara than in other urban areas of Mexico and is similar to frequencies described in the Caucasian population. On the contrary, the Huichols revealed the highest frequency of the APOE*4 allele in Mexico and in the Americas. This information could be useful for the study of dyslipidemias associated with chronic diseases and as markers of ethnic variation in the Americas.     

Variations in APOE genotype distribution in children from areas with different adult cardiovascular disease mortality in Spain

We investigate whether a varying distribution of the APOE genotype could help explain regional differences in ischemic heart disease (IHD) mortality in Spain. APOE genotypes were examined by PCR in 1,274 randomly selected healthy children from four Spanish regions with different adult IHD mortality rates (northwest and central Spain with low rates and southeast and southern Spain with high rates). In the population as a whole the prevalence of the higher risk APOE*3/*4 genotype is 16.8% and the prevalence of the APOE*4 allele is 10.1%. In northwest Spain the frequencies of the APOE*3/*4 genotype (12.9%) and of the APOE*4 allele (8.3%) are smaller than in the other regions. The southeast region shows statistically higher frequencies of the APOE*3/*4 genotype (22.5%) and of the APOE*4 allele (13.2%) than in the other regions or in the group as a whole. We can conclude that Spain is not homogeneous in terms of APOE genotype distribution. Although the prevalence of the APOE*4 allele is generally low, there are areas with higher prevalence of the APOE*4 allele and a higher incidence of adult IHD mortality. This allows us to conclude that in Spain this genetic determinant can be associated with IHD mortality in relatively isolated populations.     

APOE polymorphism in a rural older population-based sample in India

Allele frequencies are most often reported from small convenience samples of unknown demographics and limited generalizability. We determined the distribution of apolipoprotein E genotype (APOE) and allele frequencies for a large, well-defined, representative, rural, population-based sample (n = 4450) aged 55-95 years in Ballabgarh, in the northern Indian state of Haryana. The overall APOE E*2, E*3, and E*4 allele frequencies were 0.039, 0.887, and 0.073, respectively; frequencies are also reported by age, sex, and religious/caste groups. The APOE*4 frequency is among the lowest reported anywhere in the world. APOE allele frequencies did not vary significantly by age or sex in this study. To our knowledge, this is the largest Indian sample ever genotyped for the APOE polymorphism. The representativeness of the sample and its known demographics provide a much-needed normative background for studies of gene-disease associations.     

Apolipoprotein E genotyping among the healthy Kuwaiti population

Apolipoproteins (lipid-free) are lipid-binding proteins that circulate in the plasma of human blood and are responsible for the clearance of lipoproteins. Apolipoprotein E (ApoE) is one of the several classes of this protein family. It acts as a ligand for the low-density lipid (LDL) receptors and is important for the clearance of very low-density lipid (VLDL) and chylomicron remnants. The APOE gene locus is polymorphic, with three major known alleles, APOE*3, *4, and *2. We investigated the distribution of the allele frequency of the APOE gene locus and describe here the genetic variation in four Kuwaiti subpopulations: Arab origin (Arabian peninsula), Arab Bedouin tribes, Iranian origin, and the heterogeneous population. We also describe the use of Spreadex gels in resolving the amplified and digested products of the APOE gene locus. DNA was extracted from whole blood and subjected to PCR and then to RFLP analysis. Allele and genotype frequencies were estimated for the total population and for each subpopulation. Statistical analysis showed no difference in the allele frequencies between the four groups. The frequency of APOE*3 in the Kuwaiti population was highest (88.4%) followed by the frequency of APOE*4 (6.5%) and APOE*2 (5.1%). The genotype and allele frequencies obtained for the Kuwaiti population fell within the reported worldwide distribution for the APOE gene locus. Moreover, the results obtained in this study showed no statistical difference (p > 0.05) between the APOE allele and genotype frequencies between the subgroups for all six genotypes and three alleles, supporting the assumption of admixture in the Kuwaiti population and that the obtained frequencies were in Hardy-Weinberg equilibrium. Finally, we found that the distribution of the APOE alleles in Kuwait differs somewhat from those reported in other Arab populations, suggesting that the Arabs originating from the Arabian peninsula are different from those of Lebanon, Morocco, and Sudan.     

Apolipoprotein E polymorphism is related to plasma lipids and apolipoproteins in Mexican adolescents

Previous studies in the Mexican population have failed to show an effect of apolipoprotein E (APOE) polymorphism on the lipid profile. The purpose of the present study was to determine the frequencies of APOE phenotypes, and their influence on lipid and apolipoprotein levels in a random sample of Mexican adolescents living in Mexico City. APOE polymorphism, fasting insulin levels, lipid levels, and apolipoprotein levels were determined in 420 adolescents. We found a high frequency of APOE*3 subjects (89.5%) and a low frequency of APOE*2 (3.0%) and APOE*4 (7.5%) subjects. The APOE*4 subjects (including APOE 4,3 and APOE 4,4) showed the highest concentrations of total cholesterol, low-density lipoprotein cholesterol, and apoB and the lowest high-density lipoprotein cholesterol levels, whereas carriers of the APOE*2 allele (APOE 3,2 and APOE 2,2) had the lowest values for total and low-density lipoprotein cholesterol and the highest concentrations of high-density lipoprotein cholesterol. No significant differences in triglyceride and insulin levels among subjects with different APOE polymorphisms were observed. Unlike previous studies in the Mexican population, our results show that lipid and lipoprotein levels are under the influence of APOE polymorphism. As in whites, APOE*4 may be a cardiovascular risk factor in the Mexican population.     

Apolipoprotein E polymorphism in Omani dyslipidemic patients with and without coronary artery disease

Apolipoprotein E (APOE) polymorphism is a predictor of interindividual variability in plasma levels of lipids and lipoproteins and a predictor of risk of coronary artery disease (CAD). We studied the relationship between APOE polymorphism and lipid profiles and risk of CAD in Omani dyslipidemic patients. This retrospective study included 244 dyslipidemic patients, of whom 67 had CAD. Fasting blood glucose, lipids, and plasma lipoprotein levels were measured using standard methods, and APOE genotypes were detected by PCR-RFLP. The dyslipidemic patients had the following APOE allele frequencies: APOE*2, 0.030; APOE*3, 0.894; and APOE*4, 0.076. APOE allele frequencies between patients with and without CAD showed no significant differences. Compared to APOE*3/*3 homozygotes, APOE*4 allele patients had higher mean levels of low-density lipoprotein (LDL) cholesterol (p = 0.014), apoB (p = 0.031), lower mean levels of apoA1 (p = 0.043), and a trend of higher mean level of total cholesterol (p = 0.084). Thirty-one percent of patients with CAD had the APOE*4 allele compared to 26% with the APOE*3 allele, but this difference was not significant. Compared with APOE*3/*3 homozygotes, patients with the APOE*4 allele had 1.3 times higher risk for CAD after ignoring dyslipidemia, but this risk was modified after adjusting for dyslipidemia. In conclusion, among dyslipidemic patients, carriers of APOE*4 compared to homozygous carriers of APOE*3 had significantly higher levels of LDL cholesterol and apoB, but no relationship with CAD was found.     

Apolipoprotein E polymorphism in the Indian and Mestizo populations of Mexico

Apolipoprotein E (APOE) genotypes were determined in 75 Mazatecan Indians and 83 Mexican mestizos. APOE allele and genotype frequencies in Mazatecans and mestizos were similar, with high frequencies of the APOE*3 allele (0.900 and 0.915, respectively) and the E3/3 genotype (0.813 and 0.831, respectively) and an absence in both samples of the APOE*2 allele. Our data are similar to those previously described for Mexican-American and Mayan populations, which show the highest frequency worldwide of the APOE*3 allele and the E3/3 genotype. Mazatecans and mestizos also show a decreased frequency of the APOE*4 allele when compared to other Amerindian groups. The absence of the APOE*2 allele has also been reported in other Amerindian groups such as Mayans and Cayapa, whereas in Caucasians the average frequency of this allele is about 8%. Our data are in agreement with previous reports showing absence of the APOE*2 allele in Native American groups. These findings suggest that the APOE*2 allele was absent in humans from northern Asia who settled in the Arctic and populated the American continent.     

Polymorphism of the APOE locus in the Azores Islands (Portugal)

Our aim in this study is to report on the polymorphism of the APOE gene in the Azores Islands (Portugal) to obtain a population baseline of the existing variation in this locus, known to be one of the genetic determinants of plasma lipid levels. One hundred twenty-six Azorean individuals were typed for the APOE polymorphism using standard PCR-RFLP. Allele frequencies obtained for APOE*2, APOE*3, and APOE*4 were 6.75%, 83.73%, and 9.52%, respectively. The APOE*3/*3 genotype presented the highest frequency (69.84%), and the APOE*4/*4 genotype had the lowest frequency (0.79%). Genotype frequencies were in conformity with Hardy-Weinberg expectations. The observed genotype and allele frequencies were similar to those reported for other Iberian samples. Furthermore, Nei's gene diversity (H = 0.2864 +/- 0.0351) was similar to that reported for samples from mainland Portugal. The data generated from this study will be of importance in the context of ongoing studies concerning the factors that influence lipid levels in the Azorean population.     

Apolipoprotein E and presenilin-1 allelic variation and Alzheimer's disease in India

As part of a larger epidemiological survey to study the prevalence of dementia in a suburb of Mumbai, Western India, we identified 78 cases with a Clinical Dementia Rating (CDR) > or = 1.0. Of these, 49 Alzheimer's disease (AD) cases were analyzed for risk association with APOE E*4 allele at apolipoprotein E gene (APOE) and presenilin-1 (PS-1) intron-8 polymorphism and were compared with 100 age- and sex-matched nondemented controls. Genotype analysis confirmed the association of APOE E*4 allele with AD as has been reported by various studies. We report a low frequency of APOE E*4 allele, consistent with a low prevalence of AD in this study. Comparisons with other similar studies on APOE from India suggest common risk factors for AD in the Indian population, which is diverse in its ethnic and racial characteristics. The frequency for allele 1 at PS-1 intron-8 polymorphism is the highest among all studies reported. This first report of PS-1 intron-8 polymorphism and AD from India demonstrates no significant association.     

Allele frequencies of apolipoprotein E gene polymorphisms in the protein coding region and promoter region (-491A/T) in a healthy Norwegian population

This study examines the distribution of apolipoprotein E (APOE) alleles in a population of healthy male and female Norwegians (n = 798) below the age of 40. The -491A/T polymorphism of the promoter region of the APOE gene was also examined. A seminested polymerase chain reaction was applied in the genotyping. The results showed that the E3 allele had the highest frequency (0.744), followed by E4 (0.198) and E2 (0.058). The APOE frequencies found in this study differ significantly from those obtained in earlier Norwegian APOE phenotypings. The allele frequencies in the -491 site of the promoter region were 0.845 for the A allele and 0.155 for the T allele. The genotype frequency was highest for AA (0.707), followed by AT (0.277) and TT (0.016). Moreover, the A allele was in linkage disequilibrium to E4.     

Apolipoprotein E4 frequencies in a Japanese population with Alzheimer's disease and dementia with Lewy bodies

Background

The apolipoprotein E (APOE) ε4 allele has been reported to be a risk factor for Alzheimer''s disease (AD) and dementia with Lewy bodies (DLB). Previous neuropathological studies have demonstrated similar frequencies of the APOE ε4 allele in AD and DLB. However, the few ante-mortem studies on APOE allele frequencies in DLB have shown lower frequencies than post-mortem studies. One reason for this may be inaccuracy of diagnosis. We examined APOE genotypes in subjects with AD, DLB, and a control group using the latest diagnostic criteria and MRI, SPECT, and MIBG myocardial scintigraphy.

Methods

The subjects of this study consisted of 145 patients with probable AD, 50 subjects with probable DLB, and a control group. AD subjects were divided into two groups based on age of onset: early onset AD (EOAD) and late onset AD (LOAD). All subjects had characteristic features on MRI, SPECT, and/or myocardial scintigraphy.

Results

The rate of APOE4 carrier status was 18.3% and the frequency of the ε4 allele was 9.7% in controls. The rate of APOE4 carrier status and the frequency of the ε4 allele were 47% and 27% for LOAD, 50% and 31% for EOAD, and 42% and 31% for DLB, respectively.

Conclusion

The APOE4 genotypes in this study are consistent with previous neuropathological studies suggesting accurate diagnosis of AD and DLB. APOE4 genotypes were similar in AD and DLB, giving further evidence that the ε4 allele is a risk factor for both disorders.     

Apolipoprotein E and H polymorphisms in Mongolian Buryat: allele frequencies and relationship with plasma lipid levels

A Buryat population consisting of seven tribal groups in eastern Mongolia has been screened to determine the frequency distribution of different apolipoprotein E and H alleles (APOE and APOH, genes) coding for common isoforms and their association with quantitative plasma lipid levels. Allele frequencies at the APOE locus in 125 healthy Buryat aged 17 to 73 years were highest for APOE*3 (0.804), followed by APOE*4 (0.164) and APOE*2 (0.032). The APOH locus had high frequencies of APOH*2 (0.912) and APOH*3 (0.088). APOH*1 was not detected. No significant differences were observed in the overall APOE allele frequencies between the Buryat and the Siberian Evenki, Inuits, and Indians in Asia, or with some European whites. The frequency distribution of the overall APOH alleles of the Buryat was similar to that of the Japanese in Asia. Overall plasma lipid levels of the Buryat (males aged 20 to 73 years, females aged 21 to 64 years) were considerably lower, comparable to those of the Evenki. The APOE*4/E*3 males had significantly high total- and LDL-cholesterol levels compared with the APOE*3/E*3 males (p < 0.025 and p < 0.01, respectively). No significant effects of the APOH genotypes on any of the plasma lipid levels were observed. In particular, our data regarding APOE suggest that the Buryat are genetically close in allele frequencies to the Evenki and Inuits, but differ from them in the association of genotype APOE*4/E*3 with cholesterol levels.     

Apolipoprotein E polymorphism in the Netherlands and its effect on plasma lipid and apolipoprotein levels

Summary By isoelectric focusing of delipidated sera followed by immunoblotting we studied the apolipoprotein (apo) E polymorphism in 2018 randomly selected 35-years-old males from three different areas in the Netherlands. Comparison of the APOE allele (E^*2, E^*3, and E^*4) frequencies estimated in this study with those reported for several other population samples showed that there are marked differences between the Dutch population and the populations of Japan, New Zealand, Finland, and the United States. These differences in APOE allele frequencies appeared to be mainly due to differences in frequencies of the E^*2 allele (decreased in Japan and Finland; increased in New Zealand) and the E^*4 allele (increased in Finland; decreased in Japan and the United States). No difference in APOE allele frequencies was found between the Dutch population and the populations of West Germany and Scotland. Measurements of plasma cholesterol and apo B and E concentrations showed that the E^*4 allele is associated with elevated plasma cholesterol and apo B levels and with decreased apo E concentrations, whereas the opposite is true for the E^*2 allele. In the Dutch population, the sum of average allelic effects of the common APOE alleles on plasma cholesterol and apo B levels is 6.8% and 14.2%, respectively, of the total population mean. The total average allelic effect on plasma apo E concentrations was more pronounced (50.1%), suggesting that the APOE alleles primarily affect apo E concentrations rather than plasma cholesterol and apo B levels. This hypothesis is sustained by the observation that for plasma apo E levels the genetic variance associated with the APOE gene locus contributed about 18% to the total phenotypic variance. For plasma cholesterol and apo B this contribution was only 1.4% and 2.3% and is relatively low as compared with that reported for other population samples.     

Apolipoprotein B, apolipoprotein E, and angiotensin-converting enzyme polymorphisms in 2 Italian populations at different risk for coronary artery disease and comparison of allele frequencies among European populations

Polymorphisms at the apolipoprotein B (APOB XbaI, EcoRI, insertion-deletion), apolipoprotein E (APOE), and angiotensin-converting enzyme (ACE) loci are thought to be involved in susceptibility to coronary artery disease (CAD) and myocardial infarction. The aim of this study was to determine whether the allele distribution of the APOB, APOE, and ACE polymorphisms is different in 2 Italian regions with higher (northern Italy) and lower (Sardinia) CAD occurrence. The frequencies of the APOB and APOE alleles that are considered CAD risk factors were higher in northern Italy (APOB X- = 0.655; APOB R- = 0.198; APOB insertion = 0.757; APOE*4 = 0.110) than in Sardinia (APOB X- = 0.568; APOB R- = 0.159; APOB insertion = 0.680; APOE*4 = 0.052), although only APOE allele frequencies differed significantly (p = 0.001). ACE deletion allele frequencies in the 2 geographic areas showed an opposite pattern (northern Italy = 0.658; Sardinia = 0.721). Furthermore, we investigated the impact of APOB and APOE polymorphisms on interindividual variation in total cholesterol level in the 2 Italian samples, which differ in dietary habits. Only APOE phenotypes showed different mean levels of total cholesterol; the association was significant only in northern Italy (p = 0.04), where continental dietary habits and higher mean cholesterol levels prevail. These results support the suggestion that the cholesterol increasing effect of APOE*4 is environmentally mediated. Analysis of allele distributions among European populations, with remarkable differences in CAD prevalence, revealed a constant positive relationship between APOE*4 allele frequency and CAD incidence. The highest frequencies of APOB X- and R- were observed in Finland, where the incidence of CAD is high, and there is a partial agreement between APOB R- frequency and CAD occurrence across Europe, while APOB insertion and ACE deletion alleles are evenly distributed among European populations.     

Frequencies of apolipoprotein E polymorphism in a healthy Kurdish population from Kermanshah, Iran

The molecular polymorphism displayed by apolipoprotein E (APOE) has been listed as a risk factor for susceptibility to various disorders, such as those associated with lipid metabolism, arteriosclerosis, coronary artery disease (CAD), and Alzheimer disease. To evaluate the role of APOE genotypes as risk factors for Alzheimer disease, CAD, and atherosclerosis in the Kurdish population of Kermanshah, Iran, we studied the frequencies of APOE alleles *2, *3, and *4 and genotypes in 914 healthy Kurdish subjects (514 men and 400 women). The highest frequency of APOE in the Kurdish population was found for APOE*3 (87.87%). The APOE*2 and APOE*4 allele frequencies were 6.66% and 5.45%, respectively. Distribution of APOE genotypes and alleles was not significantly different between male and female subjects (p > 0.05). Interestingly, the order of the frequency of APOE alleles (*3-->*2-->*4) in the Kurdish population was quite different from that reported for most populations in the world (*3-->*4-->*2). The findings of the present study can be used to identify individuals with high risk of CAD and atherosclerosis and suggest a preventive measure to reduce their susceptibility.     

Apolipoprotein E polymorphism in India: high APOE*E3 allele frequency in Ramgarhia of Punjab

High resolution two dimensional gel electrophoresis with the combination of isoelectric focusing (IEF) and density gradient sodium dodecyl-polyacrylamide gel electrophoresis (DG-PAGE) have been employed to investigate the distribution of APOE in Ramgarhia (n = 80) and Ramdasia (n = 70) of Punjab, India. Three alleles APOE*E2, APOE*E3 and APOE*E4 were observed in Ramgarhia and Ramdasia with the frequencies of 0.031, 0.913, 0.056 and 0.043, 0.886 and 0.071, respectively. Higher heterozygosity (20.8%) in Ramdasia reflects greater variation at the APOE locus. The APOE*E3 allele is found to be the highest (0.913) in Ramgarhia in comparison to forty-one populations of the world. A decreasing cline from south to north was evident for *E2 and *E4 allele frequencies (y = -0.002x + 0.141, r = 0.78 and y = -0.004x + 0.229, r = 0.83, respectively, and an increasing cline for the *E3 allele towards north was observed (y = 0.006x + 0.629, r = 0.82) in Asia.     

Parkinson's disease and apolipoprotein E: possible association with dementia but not age at onset

Idiopathic Parkinson's disease (PD) is an age-dependent, neurodegenerative condition frequently associated with dementia. Although it is predominantly a sporadic disease, 20-30% of cases are familial, suggesting a complex mode of inheritance. Apolipoprotein E (APOE) allele epsilon4 has been associated with familial and sporadic late-onset senile dementia of the Alzheimer's type. To investigate the role of this gene in the development of dementia associated with PD and age at onset of PD, we evaluated the frequency of APOE gene polymorphism in a sample of PD patients with (n=118) and without (n=167) a family history, as well as matched normal controls (n=96). The PD sample was categorized according to age at onset and presence or absence of dementia. Kaplan-Meier survival analysis was used to plot genotype-specific age at onset distribution curves. Allele frequencies of APOE in PD patients with and without a family history and normal controls were not significantly different. APOE genotypes were also similar between the groups. However, the frequencies of epsilon4 allele and epsilon4/- genotype in the PD group with dementia were more than twofold higher than in normal controls, and the differences were statistically significant. There were no differences in the allele and genotype frequencies of the APOE gene between PD groups with different age at onset. The familial PD had significantly earlier age at onset than sporadic PD (Log-rank test, P=0.027). The age at onset distribution curves for different genotype groups were similar, and their differences were not statistically significant (P=0.38). After the Bonferroni's correction for multiple tests, the positive results are not significant at the P<0.05 level. We conclude that APOE does not play an important role in susceptibility to PD or age at onset of PD, but may play a role in dementia associated with PD in our sample.     

Association of apolipoprotein E but not B with Alzheimer's disease

In our studies apolipoprotein E4 (APOE4) is associated with both early- and late-onset Alzheimer's disease. Alzheimer's patients from West Texas were screened for the APOE4 allele, which was found at frequencies of 0.43 and 0.59 in familial late- and early-onset cases. Sporadic cases had lower frequencies, but they still were 2–4 times higher than control spouses. To determine whether the APOE association may be a risk factor for coronary disease as well, we examined two APOB gene restriction sites that have previously been found to be associated with coronary artery disease, especially myocardial infarctions. The APOB alleles were found at similar frequencies in Alzheimer's patients and control spouses.     

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.     

Haplotype analysis of the apolipoprotein E and apolipoprotein C1 loci in Portugal and São Tomé e Príncipe (Gulf of Guinea): linkage disequilibrium evidence that APOE*4 is the ancestral APOE allele

The joint distributions of phenotypes from the apolipoprotein E gene (APOE) and from a closely linked restriction site polymorphism at the apolipoprotein C1 locus (APOC1) were studied in population samples from Portugal and S?o Tomé e Príncipe (Gulf of Guinea), a former Portuguese colony that was originally populated by slaves imported from the African mainland. The frequencies of the APOE alleles (*2, *3, and *4) in Portugal and S?o Tomé fitted the ranges of variation generally observed in European and African populations, respectively. Haplotype analysis showed that in both populations the strength of linkage disequilibrium was highest for the APOE*2 allele and lowest for the APOE*4 allele, suggesting that the origin of the APOE alleles followed a 4-->3-->2 pathway and thus providing independent confirmation of the results from sequence homology studies with nonhuman primates. In accordance with global trends in the distribution of human genetic variation, the European sample from Portugal presented more intense linkage disequilibrium between APOE and APOC1 than the African sample from S?o Tomé where, despite the short 4-kb distance that separates the 2 loci, the level of association between the APOC1 alleles and APOE*4 was nonsignificant.