Apolipoprotein E Gene Polymorphism and Allele Frequencies in the Lebanese Population

Apolipoprotein E (ApoE) genotypes were studied in order to determine the prevalence in the Lebanese population and compare it with other populations. DNA from 160 unrelated healthy donors from our HLA-bank was used. ApoE genotype was determined using the CardioVascular Disease (CVD) StripAssay (this assay is based on a Polymerase Chain Reaction-Reverse Hybridization technique). The prevalence of genotypes E3/3, E3/4, and E2/3 was found to be 69%, 26%, and 22%, respectively, and 0.6% for each of E2/4 and E4/4 genotypes. The Lebanese population tested showed similarities to earlier reported ApoE genotypic distributions (high E3 allele frequency) but also peculiar differences especially to some Arabic countries (total absence of E2 allele among Saudis) and other populations. This is the first report from Lebanon that will serve as a template for future investigations of the prevalence of ApoE alleles in association with various clinical entities.     

Analysis of Apolipoprotein E Gene Polymorphism in Populations of the Volga–Ural Region

Polymorphism at the apolipoprotein E gene (apoE) in populations of the Volga–Ural region was studied by means of polymerase chain reaction. In the region examined the population-specific patterns of the apoE alleles and genotypes frequency distribution were established. The results obtained were compared with the literature data on the apoE polymorphism in other world populations. Substantial heterogeneity of different ethnic populations in respect to the apoE genotypes distribution and frequency was revealed.     

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.     

Apolipoprotein E gene polymorphisms in Lebanese with hypercholesterolemia

Apolipoprotein E (ApoE) has an important role in the metabolism of lipids through its major isoforms (ε2, ε3, ε4). In particular, ApoE ε4, has been considered as a major genetic risk factor for cardiovascular diseases (CVD). The aim of our study is to investigate the frequency of ApoE gene polymorphisms (rs 429358C > T, rs 7412C > T) and their relationship to lipid parameters in a group of Lebanese hypercholesterolemic subjects (22 males and 24 females, aged 25–80 years). Lipid profile, apolipoproteins A-I and B were determined using fasting serum samples; and molecular analysis of ApoE polymorphisms using blood in EDTA tubes. The distribution of the four ApoE genotypes detected in this study was: ε3/ε3 (73.9%), ε3/ε4 (17.4%), ε2/ε3 (6.5%), and ε2/ε4 (2.2%) resulting in allelic frequencies for ε2, ε3 and ε4 of 4.3%, 85.9% and 9.8%, respectively. No association was determined among any of the lipid parameters, gender and ApoE genotypes. Lipid parameters were not statistically different among various ApoE genotypes (p > 0.05). ApoE ε2 frequency was found to be lower than that previously reported for healthy Lebanese (7.2%). CVD is one of the major leading causes of mortality in Lebanon with a reported prevalence of 12.2% in males and 7.7% in females, which incidentally agrees with our finding regarding ε4 allelic frequency of 13.6% in males and 6.3% in females. Consequently, larger prospective studies are recommended to highlight the correlation of ApoE polymorphisms to other biochemical and environmental factors involved in CVD.     

Apolipoprotein E (ApoE) polymorphism is related to differences in potential fertility in women: a case of antagonistic pleiotropy?

The alleles that are detrimental to health, especially in older age, are thought to persist in populations because they also confer some benefits for individuals (through antagonistic pleiotropy). The ApoE4 allele at the ApoE locus, encoding apolipoprotein E (ApoE), significantly increases risk of poor health, and yet it is present in many populations at relatively high frequencies. Why has it not been replaced by natural selection with the health-beneficial ApoE3 allele? ApoE is a major supplier of cholesterol precursor for the production of ovarian oestrogen and progesterone, thus ApoE has been suggested as the potential candidate gene that may cause variation in reproductive performance. Our results support this hypothesis showing that in 117 regularly menstruating women those with genotypes with at least one ApoE4 allele had significantly higher levels of mean luteal progesterone (144.21 pmol l⁻¹) than women with genotypes without ApoE4 (120.49 pmol l⁻¹), which indicates higher potential fertility. The hormonal profiles were based on daily data for entire menstrual cycles. We suggest that the finding of higher progesterone in women with ApoE4 allele could provide first strong evidence for an evolutionary mechanism of maintaining the ancestral and health-worsening ApoE4 allele in human populations.     

Analysis of the angiotensinogen gene T174M polymorphism in populations of the Volga-Ural region

The method of polymerase chain reaction was used to analyze T174M polymorphism at the angiotensinogen (AGT) gene in a number of populations of the Volga-Ural region, belonging to Finno-Ugric (Komi-Permyaks, Maris, Mordovians, and Udmurts), Turkic (Chuvashes, Tatars, and Bashkirs), and Eastern-Slavic (Russians) ethnic groups. Population-specific patterns of the polymorphic alleles and genotypes frequency distribution were established. Comparison of the results with the literature data on the AGT gene polymorphism in different world populations provided identification of specific trends in the changes of genotype frequency of the AGT gene depending on the ethnicity of the populations.     

Is the ApoE polymorphism associated with dilated cardiomyopathy?

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

Molecular-genetic analysis of polymorphism of the DXS532 locus in people from the Volga-Ural region]

The DXS52 polymorphic locus mapping to the 5'-region of the blood-clotting factor VIII gene on the X chromosome was genotyped in seven Volga-Ural ethnic groups (Bashkirs, Tatars, Chuvashes, Maris, Mordovians, Udmurts, and Komis). A total of 47 different genotypes and 15 allelic variants of this locus were described. Substantial intra- and interpopulation heterogeneity of the ethnic groups studied in respect to frequency and distribution of the DXS52 alleles and genotypes was demonstrated. The unimodal DXS52 allele frequency distribution pattern with the peak at 1690 bp was typical to Mordovians and Komis. Chuvashes and Maris, as well as Udmurts, were characterized by bimodal frequency distribution patterns, with the peaks at 1690 and 670 bp, and 1690 and 1390 bp, respectively. Moreover, Bashkirs and Tatars displayed trimodal DXS52 allele frequency distribution patterns with the peaks at 1690, 1390, and 670 bp. The DXS52 allele frequency distribution patterns described in populations of the Volga-Ural region were found to be remarkably different from those established for the mixed Moscow population and the population of Western Europe. These data indicate that the DXS52 locus is highly informative, and this polymorphic system can serve as a molecular marker for population genetic studies.     

Analysis of the Angiotensinogen Gene T174M Polymorphism in Populations of the Volga–Ural Region

The method of polymerase chain reaction was used to analyze T174M polymorphism at the angiotensinogen (AGT) gene in a number of populations of the Volga–Ural region, belonging to Finno–Ugric (Komi-Permyaks, Maris, Mordovians, and Udmurts), Turkic (Chuvashes, Tatars, and Bashkirs), and Eastern-Slavic (Russians) ethnic groups. Population-specific patterns of the polymorphic alleles and genotypes frequency distribution were established. Comparison of the results with the literature data on the AGT gene polymorphism in different world populations provided identification of specific trends in the changes of genotype frequency of the AGT gene depending on the ethnicity of the populations.     

Analysis of polymorphism of CTG repetitive sequences in the gene of myotonic dystrophy in human populations of the Volga-Ural region]

Distribution of CTG repetitive sequences in the myotonic dystrophy (MD) gene was analyzed in ten populations of the Volga-Ural region, including Tatars, Chuvashes, Maris, Udmurts, Mordovians, Komis, and four ethnogeographical groups of Bashkirs. A total of 25 alleles were found (9 to 14 in individual populations), with each allele containing 5 to 34 trinucleotide repeats. The allele frequency distribution had two peaks corresponding to alleles with 5 and 11-14 CTG repeats. The frequency of the (CTG)5 allele varied from 0.23 to 0.47 in Maris and Mordovians, respectively. Regarding the (CTG)11-14 alleles, those containing 13 and 12 trinucleotides were most frequent in all populations; their frequencies varied from 0.15 in Mordovians to 0.24 in Maris and Bashkirs from the Abzelilovskii raion (district). Alleles with large numbers of repeats (more than 30) were only found in Tatars and Bashkirs from the Abzelilovskii raion, where their frequency was 0.01. The data obtained were compared with those on other human populations from various regions of the world. In general, the populations of the Volga-Ural region took an intermediate position between European and Asian populations (although were somewhat more similar to the latter ones) with respect to the distribution of allelic frequencies of the CTG repetitive sequences. In individual populations, the number of genotypes varied from 13 to 27 in Mordovians and Bashkirs from the Ilishevskii raion, respectively. The observed heterozygosity was the highest (91%) in Udmurts and the lowest (58%) in Mordovians; the average heterozygosity was 81%. Such a high heterozygosity, as well as the revealed differentiation of the populations with respect to the distribution of the allelic frequencies of CTG repetitive sequences in the MD gene, allow this polymorphic DNA locus to be considered a highly informative genetic marker of populations.     

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.     

Apolipoprotein E polymorphism in normal Han Chinese population: frequency and effect on lipid parameters

Apolipoprotein E (ApoE) genotypes were studied in order to determine the prevalence and effect on lipid parameters in normal Han Chinese population. Fragments of ApoE gene forth exon containing codon 112 and 158 polymorphic locus were amplified by PCR, and then digested with Cfo I endonuclease. Genotypes and alleles frequencies of 168 healthy Han Chinese were calculated. The frequency of genotypes ε3/3, ε3/4, and ε2/3 was found to be 75.00, 10.70, and 11.90%, respectively, and 0.60, 1.20, and 0.60% for ε2/2, ε2/4, and ε4/4. The effects of ApoE genotypes and alleles on lipid parameters were analyzed. The effects of ApoE alleles on TC, LDL-C, ApoB was: along a decreasing gradient ε4 > ε3 > ε2. The effect of ε4 allele was to increase serum levels of TC, LDL-C and ApoB, and ε2 allele had an effect opposite to that of ε4 allele. Results obtained in this study indicate that ApoE polymorphism is an independent genetic factor on individual serum levels of lipids and apolipoproteins. Shu Liang and Min Pan should both be considered first authors.     

Identification of HCV genotypes in HCV infected blood donors

HCV infection is a leading cause of chronic liver disease, including cirrhosis of the liver. There are at least six major genotypes and more than 50 subtypes of HCV. The prevalence and distribution of HCV genotypes depend on geographical location. The aim of this study was to identify and compare the HCV genotypes in HCV infected blood donors and patients. In this cross-sectional study, 167 serum samples from 103 blood donors and 64 patients with hepatitis C were investigated for HCV genotypes. HCV genotyping was carried out using type-specific primers from the core region of the viral genome. The highest frequency was for genotype 1a, with 53 and 34 (51.5% versus 53.1%) of subjects in blood donors and patients respectively. Genotype 3a and 1b were the other frequent genotypes with 4 and 16 (3.9% versus 25%) and 39 and 10 (37.9% versus 15.6%) subjects, respectively. There was not any statistical significant association between the place of infection of the patients and genotype. The results of this study indicate that the distribution of genotypes in the two populations was similar. The dominant HCV genotypes between blood donors and patients were 1a, 3a and 1b respectively.     

Apolipoprotein E polymorphism in relation to plasma lipid levels and other risk factors of atherosclerosis in two ethnic groups from Slovakia

The influence of apolipoprotein E (ApoE) genotypes on plasma lipid levels and interaction with other environmental factors was determined in two Slovakian population samples; 146 Romany and 351 Slovak individuals. The two samples differ significantly in the distribution of E3/3 genotypes (p<0.014) and E3/2 (p<0.035). Analysis of variance did not reveal any significant effect of the ApoE genotypes on any of the plasma lipid levels in the Romany individuals. In the Slovak sample the variation in plasma low-density lipoprotein cholesterol (LDL-C) levels was significantly associated with the ApoE genotypes (p=0.012). We detected decreased LDL-C concentrations in males with E2 genotype when compared with E3 and E4 carriers (p=0.008). Further, the E2 genotype was found to be associated with high triglycerides levels (p=0.009). The ethnic samples differ significantly in the prevalence of metabolic syndrome and in the case of males of diabetes. Both the Romany and the Slovak males can be considered as having a more atherogenic profile compared with the females.     

VNTR-polymorphism of the PAH, e-NOS genes and deletion of the CCR5 gene in populations in the northern Caucasus

VNTR allelic polymorphism at the phenylalanine hydroxilase (PAH) and endothelial constitutive nitric oxide synthase (eNOS) genes and the prevalence of the CCR5 chemokine receptor gene 32-bp deletion were examined in four indigenous populations of Northern Caucasus, Adygs, Kumyks, Karachais, and Nogais (Kuban and Karanogais). Population-specific features of the allele and genotype frequency distribution patterns of the polymorphisms examined were described. The data obtained were compared to those obtained from literature. The results of the study confirmed that the frequency and occurrence of the PAH polymorphic alleles exhibit substantial interpopulation differences. In the populations of Northern Caucasus, the eNOS minisatellite polymorphism alleles and genotypes frequency distribution patterns were close to those described earlier for populations of the Volga-Ural region (VUR), and also for the Australian Caucasoids, Japanese, and Turks. In the populations examined, the mean frequency of the CCR5 gene deletion was 0.055, which was somewhat lower than in the populations of VUR (0.07) and Europe (0.081), and practically identical to that in Asian populations (0.050). For each population observed and expected heterozygosities at each locus were calculated. In general, the gene pool of Northern Caucasian populations showed substantial differentiation at the loci examined: the GST value was 0.0274. The data for individual loci showed that the greater contribution to the interpopulation diversity was made by the differences in the PAH VNTR allele frequencies (GST = 0.04), while the differences at the eNOS and CCR5 loci were small (GST = 0.0025 and GST = 0.0039, respectively).     

Contributions of 18 additional DNA sequence variations in the gene encoding apolipoprotein E to explaining variation in quantitative measures of lipid metabolism

Apolipoprotein E (ApoE) is a major constituent of many lipoprotein particles. Previous genetic studies have focused on six genotypes defined by three alleles, denoted epsilon2, epsilon3, and epsilon4, encoded by two variable exonic sites that segregate in most populations. We have reported studies of the distribution of alleles of 20 biallelic variable sites in the gene encoding the ApoE molecule within and among samples, ascertained without regard to health, from each of three populations: African Americans from Jackson, Miss.; Europeans from North Karelia, Finland; and non-Hispanic European Americans from Rochester, Minn. Here we ask (1) how much variation in blood levels of ApoE (lnApoE), of total cholesterol (TC), of high-density lipoprotein cholesterol (HDL-C), and of triglyceride (lnTG) is statistically explained by variation among APOE genotypes defined by the epsilon2, epsilon3, and epsilon4 alleles; (2) how much additional variation in these traits is explained by genotypes defined by combining the two variable sites that define these three alleles with one or more additional variable sites; and (3) what are the locations and relative allele frequencies of the sites that define multisite genotypes that significantly improve the statistical explanation of variation beyond that provided by the genotypes defined by the epsilon2, epsilon3, and epsilon4 alleles, separately for each of the six gender-population strata. This study establishes that the use of only genotypes defined by the epsilon2, epsilon3, and epsilon4 alleles gives an incomplete picture of the contribution that the variation in the APOE gene makes to the statistical explanation of interindividual variation in blood measurements of lipid metabolism. The addition of variable sites to the genotype definition significantly improved the ability to explain variation in lnApoE and in TC and resulted in the explanation of variation in HDL-C and in lnTG. The combination of additional sites that explained the greatest amount of trait variation was different for different traits and varied among the six gender-population strata. The role that noncoding variable sites play in the explanation of pleiotropic effects on different measures of lipid metabolism reveals that both regulatory and structural functional variation in the APOE gene influences measures of lipid metabolism. This study demonstrates that resequencing of the complete gene in a sample of >/=20 individuals and an evaluation of all combinations of the identified variable sites, separately for each population and interacting environmental context, may be necessary to fully characterize the impact that a gene has on variation in related traits of a metabolic system.     

The relationship between genetic polymorphisms in apolipoprotein E (ApoE) gene and osteonecrosis of the femoral head induced by steroid in Chinese Han population

Previous studies suggested that apolipoprotein E (ApoE) genetic polymorphisms (SNPs) may result in abnormal lipid metabolism. Therefore, genetic polymorphisms in ApoE may be associated with the occurrence of osteonecrosis of the femoral head (ONFH). A case control study was designed to include 580 patients with steroid-induced ONFH and 560 age- and sex-matched non steroid-induced ONFH control subjects to analyze the association between ApoE polymorphisms and susceptibility of steroid-induced ONFH. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was utilized to differentiate two genotypes SNPs (rs7412 C/T and rs429358 T/C) in ApoE gene. Both rs7412 C/T and rs429358 T/C were found to be associated with the risk of steroid-induced ONFH. However, no significant association was observed between the haplotypes T-T, T-C and C-C in ONFH. Furthermore, T allele of rs7412 and C allele of rs429358 carriers were associated with higher levels of TG in steroid-induced ONFH patients (P?<?0.05). The study suggested that ApoE genetic polymorphisms conferred susceptibility to steroid-induced ONFH in Chinese Han population. However, the results need further investigation with large sample size and various populations.     

Molecular-genetic analysis of VNTR polymorphism in alleles of the phenylalanine hydroxylase gene in inhabitants of the Volga-Urals region

Molecular genetic analysis of the VNTR alleles at the phenylalanine hydroxylase (PAH) gene was carried out in seven Volga-Ural ethnic groups (Bashkirs, Tatars, Chuvashes, Maris, Mordovians, Udmurts, and Komis). The PCR fragments revealed included alleles of 380, 440, 470, 500, 530, 560, and 650 bp, containing 3, 5, 6, 7, 8, 9, and 12 repeat copies, respectively. Substantial heterogeneity of the populations in respect to the distribution and frequency of the VNTR alleles and genotypes was demonstrated. The indices of observed and theoretical heterozygosity of the PAH VNTR alleles were calculated. The mean heterozygosity index was 70.02%. This high index value along with the established differentiation of the populations in respect to the frequency distribution of the VNTR alleles and PAH genotypes permitted the conclusion that the given polymorphic locus can serve as a highly informative marker for examination of the genetic structure of the Volga-Ural populations.     

Glutathione S-transferase T1 (GSTT1) and M1 (GSTM1) polymorphisms in a sample of the population in Northern Italy

Glutathione S-transferase is a group of multifunctional enzymes important in the metabolism of xenobiotics. GSTT1 and GSTM1 are polymorphic in human populations. Since a relation between polymorphism and cancer susceptibility has been found, their distribution in human populations is of great interest. In the present study the distribution of GSTT1 and GSTM1 genotypes was studied in a total sample of 252 individuals of three localities of north-west Italy (Postua, Cavaglià and Biella) by PCR test. The frequencies of GSTT1 and GSTM1 "null" genotypes were respectively 7.94% and 34.92%. There are no significant differences between the populations studied in the GSTT1 "null" genotypes. On the other hand, for GSTM1 the frequency of gene deletion in Postua (25.5%) differs significantly (p < 0.01; chi-square test) from that of Biella (46.32%), which approaches the values indicated by most studies for Europeans (about 50%). The analysis of the frequencies of GSTT1 and GSTM1 polymorphisms among different age groups showed a lower frequency of negative genotypes in the older group, although not statistically confirmed.     

Apolipoprotein E polymorphism in elderly Japanese-Brazilian immigrants does not explain the reduced cardiovascular risk factor incidence

Study of immigrant populations may contribute to a better understanding of the epidemiology of diseases associated with the aging process. We examined the prevalence of cardiovascular risk factors, including apolipoprotein E (ApoE) polymorphism, in elderly subjects who were born in Japan, migrated to South Brazil and have lived in that region for over 40 years, versus a group of elderly, locally born Brazilians living in the same region. These Japanese subjects came to Brazil after World War II (1950-1960) from several Japanese cities, mainly Nagasaki, Kumamoto and Hokkaido. Among 1007 subjects genotyped for ApoE polymorphism, we selected 540 elderly subjects (>60 years old), consisting of 270 Japanese-Brazilians and 270 Brazilians of European ancestry from Rio Grande do Sul State (Gaucha population). The Japanese-Brazilian group had significantly lower prevalences of obesity, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome than did the Gaucho population group. ApoE polymorphism frequencies were similar in the two groups. The differences in cardiovascular risk factors observed in the two populations cannot be explained by ApoE polymorphism; they could be related to conservation of Japanese lifestyle habits, such as diet.