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 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.     

Genetic studies of human apolipoproteins. XVIII. Apolipoprotein polymorphisms in Australian Aborigines

A tribal aboriginal community, the Mowanjum, from the Kimberley region in Western Australia has been screened to determine the extent of genetic variation in the products of genes coding for apolipoproteins, which are intimately involved in lipid metabolism. Of the seven systems tested, APOE and APOH revealed common structural variations, but their distribution patterns are significantly different from those found in European populations. Australian Aborigines were found to be unique because they have no APOE*2 and APOH*3 alleles and have strikingly high frequencies of the APOE*4 (26%) and APOH*1 (13%) alleles. The contrast in variation observed at these apolipoprotein loci between Australian Aborigines and Europeans not only makes these loci useful genetic markers in biologic anthropology studies but also provides a unique opportunity to investigate the role of genetic-environment interaction in determining interpopulation differences in cardiovascular disease risk factors.     

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 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 H genetic variability in the population of Krk Island,Croatia

Apolipoprotein polymorphisms are emerging as suitable markers for the study of the formation of human populations. In contrast to the data available for apolipoprotein E, the data regarding apolipoprotein H (protein, apoH; gene, APOH) variations are only beginning to accumulate. By blood plasma isoelectric focusing and immunoblotting, we analyzed the distribution of apoH phenotypes in 397 individuals (192 males; 205 females) from seven villages of an autochthonous population of the eastern Adriatic island of Krk. APOH allele frequencies were: APOH*2 = 0.877, APOH*3 = 0.098, APOH*1 = 0.025, with the majority of the sample being homozygous. No significant differences between villages were observed. When these data were compared to those of other populations studied so far, a significant association between APOH allele frequencies and latitude was observed. We hypothesize that this association reflects differences in diet composition across different climatic zones.     

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 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.     

Genetic variation in the apolipoprotein H (β2-glycoprotein I) gene affects plasma apolipoprotein H concentrations

Apolipoprotein H (apoH, protein; APOH, gene) is a single chain glycoprotein that exists in plasma both in a free form and in combination with lipoprotein particles. ApoH has been implicated in several physiologic pathways, including lipid metabolism, coagulation, and the production of antiphospholipid antibodies. The wide range of interindividual variation in plasma apoH levels is thought to be under genetic control, but its molecular basis is unknown. APOH displays a common structural polymorphism with the occurrence of three common alleles (APOH*1, APOH*2, and APOH*3), the APOH*2 allele being the most frequent in all populations. The relationship between the APOH polymorphism and plasma apoH levels is unknown. In this study, we have determined the impact of this APOH polymorphism on apoH levels in 455 normoglycemic non-Hispanic Whites (220 men and 235 women) from the San Luis Valley, Colorado. Mean plasma apoH levels, determined by capture enzyme-linked immunosorbent assay, were 20.0±0.2 mg/dl (range: 3.4–31.2 mg/dl) with no significant difference between men and women. In women, but not in men, age had a significant effect on plasma apoH levels explaining 3.4% of its phenotypic variance. ApoH levels also correlated positively with cholesterol (P=0.015), HDL-cholesterol (P=0.044), and triglyceride (P=0.037) in women, but not in men. An analysis of variance (ANOVA) of adjusted plasma apoH levels showed significant association with the APOH polymorphism in both men and women (P<0.0001), and the APOH polymorphism accounted for 11.4% and 13.6% of the variation in apoH levels in men and women, respectively. Compared with the APOH*1 and APOH*2 alleles, the APOH*3 allele was associated with significantly lower plasma apoH levels. At the molecular level, APOH*3 can be further subdivided into two distinct forms, called APOH*3 ^W and APOH*3 ^B . The APOH*3 ^W form is more common in US Whites and is the result of a missense mutation at codon 316. An ANOVA for the codon 316 polymorphism revealed that this polymorphism is a major determinant of plasma apoH variation (P<0.0001). This study indicates that common genetic variation in the APOH gene is a significant determinant of plasma apoH levels in non-Hispanics Whites and should be useful in evaluating the role of the APOH genetic variation in various metabolic pathways in which apoH has been implicated. Electronic Publication     

Genetic variation of apolipoproteins in North Indians

Genetic variation at three apolipoprotein loci (APOA4, APOH, and APOE) has been examined in nine endogamous populations of Punjab, North India. The overall pattern of allele frequency variation at different loci is compatible with that of European populations, but observed microvariation differentiates the populations according to their position in the Indian caste structure. The most common allele at the APOA4 locus was APOA4*1 with a narrow frequency range (89%-92%). APOH*2 allele frequency was highest in these populations (0.852-0.914). APOE*E4 allele frequency was relatively low (6%-10%) in the North Indian populations compared to its frequency in many European populations. The anthropological usage of these polymorphisms was evaluated using multivariate analyses. Genetic distance analysis and principal correspondence analysis showed that the North Indian populations are closest to Europeans, followed by Chinese and African populations. Overall, this study highlights the usefulness of apolipoproteins as genetic markers for clinical, population, and anthropological studies.     

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 and its association with serum lipid levels in Brazilian children

The influence of apolipoprotein E (APOE) genotypes on plasma lipid levels was determined in 414 Brazilian healthy children of mixed ethnicity, age 5 to 15 years (mean 8.9+/-2.9). The APOE*3 allele was the most frequent (77%), followed by APOE*4 (17%) and APOE*2 (6%). The pattern of lipid differences among genotypes was similar in both boys and girls. We did not detect an increase in cholesterol levels with the presence of the APOE*4 allele. Because a growing body of evidence suggests that the effect of *4 depends on its interaction with diet, the frequency of *4 might be more variable in children than in adults as well as among populations. Children carrying a *2 allele had lower total cholesterol (TC) and LDL-cholesterol levels (138.47+/-24.32 and 77.72+/-19.42, respectively) compared with *3/*3 children (158.33+/-25.28 and 97.05+/-21.82, respectively). Mean TC/HDLC ratio was also lower in children with the APOE*2 allele (3.27+/-0.66 versus 3.64+/-0.76). In this highly admixed population sample, the *2 anti-atherogenic lipid pattern is already detected in children.     

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.     

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.     

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.     

Polymorphism of the Apolipoprotein B Gene and Association with Plasma Lipid and Lipoprotein Levels in the Mongolian Buryat

Allele frequencies at six RFLP sites (Ins/Del, ApaLI, AluI, XbaI, MspI, and EcoRI) of the apolipoprotein B gene (APOB) and the relationship of genotypes with plasma lipid and lipoprotein levels in the Mongolian Buryat were investigated. Common alleles at these sites in 110 Buryat subjects were I, G, A-, X-, M+, and E+; the frequencies of 0.809-0.991 differed strikingly from those of a few Asians and most Europeans. Five unambiguous haplotypes of all sites were revealed at 74%; haplotype IGA-X-M+E+ (000000) was the most frequent (67%), followed by IGA+X-M+E+ (001000) (19%). The frequency constitution differed significantly from the Chinese, Malaysians, and Caucasians but resembled the Indians. No APOB polymorphisms were associated with cholesterol levels (total, HDL and LDL). Significant associations of genotypes were shown with the triglyceride level only at the AluI and XbaI sites. The lipid level of A-A+ females or X-X+ males was higher than that of A-A- females or X-X- males, respectively.     

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.     

Molecular basis of the apolipoprotein H (β2-glycoprotein I) protein polymorphism

Apolipoprotein H (apoH, protein; APOH, gene) is considered to be an essential cofactor for the binding of certain antiphospholipid autoantibodies to anionic phospholipids. APOH exhibits a genetically determined structural polymorphism due to the presence of three common alleles (APOH*1, APOH*2 and APOH*3 ) detectable by isoelectric focusing (IEF) and immunoblotting. The APOH*3 allele can be further characterized into two subtypes, APOH*3^W and APOH*3^B, based upon its reactivity with monoclonal antibody 3D11. In this study we have determined the molecular basis of the APOH protein polymorphism and its distribution in three large U.S. population samples comprising 661 non-Hispanic whites, 444 Hispanics and 422 blacks. By direct DNA sequencing of PCR amplified fragments corresponding to the eight APOH exons, we identified two missense mutations that correspond to the APOH*1 and APOH*3^W alleles. A missense mutation (G→A) in exon 3, which alters amino acid Ser to Asn at codon 88 and creates a restriction site for TSP509 I, was present in all APOH*1 allele carriers. A second missense mutation (G→C) at codon 316 in exon 8, which replaces amino acid Trp with Ser and creates a restriction site for BSTBI, was present in all APOH*3^W carriers. The distribution of the Ser 88 Asn and Trp 316 Ser mutations was significantly different between the three racial groups. The frequency of the Asn-88 allele was 0.011, 0.043, and 0.056 in blacks, Hispanics and non-Hispanic whites, respectively. While the Ser-316 allele was observed sporadically in blacks (0.008), it was present at a polymorphic frequency in Hispanics (0.027) and non-Hispanic whites (0.059). The identification of the molecular basis of the APOH protein polymorphism will help to elucidate the structural – functional relationship of apoH in the production of antiphospholipid autoantibodies. Received: 20 November 1996 / Accepted: 13 February 1997     

Apolipoprotein E Polymorphism and Plasma Lipid Levels in Native Mongolian Sheep

Apolipoprotein E (apoE) phenotypes were determined in 199 unrelated native sheep (Khalkhas line) of Central Mongolia, using a polyacrylamide gel isoelectric focusing-immunoblotting technique, and the plasma lipid levels in different phenotypes were assayed enzymatically. Twenty-eight phenotypes were identified in this sheep. In addition to all the previously detected seven apoE variants composing the phenotypes, four new variants were discovered, which were called E8, E9, E10, and E11. From the population data, these were found to be genetically controlled by four codominant alleles, designated APOE8, APOE9, APOE10, and APOE11, based on the same mode of inheritance as in the seven variants. These alleles were detected at a low frequency, in the range of 0.005 to 0.0126. The Khalkhas sheep differed most significantly from the Baruwal and Lampuchhre sheep of Nepal and the Vietnamese sheep with respect to the allele frequencies found in some Asian local sheep previously examined. Type 1/1 and/or 2/7 sheep had significantly higher plasma levels of total cholesterol and low-density lipoprotein cholesterol than type 7/7 sheep (P < 0.05 and/or P < 0.02).     

Apolipoprotein A-IV polymorphism and its effect on plasma lipid and apolipoprotein concentrations

Recently, we determined the apolipoprotein E (apoE) phenotype distribution in 2,000 randomly selected 35-year-old male individuals by slab gel isoelectric focusing of delipidated plasma samples, followed by immunoblotting using anti-apoE antiserum. These blots have been successfully re-used for immunovisualization of apoA-IV isoelectric focusing patterns. In a population sample of 1,393 individuals, four distinct apoA-IV isoforms were detected, encoded by the alleles A-IV*0, A-IV*1, A-IV*2, and A-IV*3 with gene frequencies of 0.002, 0.901, 0.079, and 0.018, respectively. The mean of plasma cholesterol, triglyceride, apoB and E levels did not differ significantly among the different apoA-IV phenotype groups. For these lipoprotein parameters, less than 0.1% of the total phenotypic variance could be accounted for by the APOA-IV gene locus. Our results did not show any effect of apoA-IV polymorphism on plasma apoA-I levels nor could we find any correlation between plasma levels of apoA-I and apoA-IV within the different apoA-IV phenotype groups. The plasma level of apoA-IV in subjects bearing the A-IV*3 allele is significantly lower than in subjects without the A-IV*3 allele (5 mg/dl versus 14 mg/dl). We therefore conclude that, in contrast to the apoE polymorphism, the polymorphism at the APOA-IV locus does not influence any of the levels of the lipoprotein parameters considered except apoA-IV.