Apolipoprotein E and A-IV Polymorphisms in Ethnic Russians Living in Estonia

To determine the distribution of genetic variations in apolipoprotein E (apoE) and apolipoprotein A-IV (apoA-IV) genes, 137 Russians living in Estonia was screened by isoelectric focusing and immunoblotting procedures. The apoA-IV-2 allele and apoE4 allele frequency of the Russians tended to be lower than in most other European populations.     

Polymorphism of the apolipoprotein E gene and risk of multiple sclerosis in ethnic Russians

Multiple sclerosis (MS) is a multifactorial disease of the central nervous system with pronounced hereditary predisposition. The purpose of the study was to test the assumption on the involvement of the apolipoprotein E gene (APOE) polymorphism in exon 4 in the development of MS in ethnic Russians. Samples independently collected in Moscow (106 MS cases and 189 control healthy volunteers), Sverdlovsk oblast (54 and 109, respectively), and the Republic of Bashkortostan (119 and 285, respectively) were examined. Genotypes for 2059C/T and 2197C/T polymorphisms of the APOE gene, which determine the amino acid substitutions C112R and R158C in apolipoprotein E, were analyzed by polymerase chain reaction followed by restriction analysis of amplificates. No statistically significant differences in genotype or allele frequencies were found between the control group and the group of MS cases. The APOE*4 allele is not associated with the risk of MS in ethnic Russians.     

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

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

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

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

Variability of the 3'APOB minisatellite locus in Eastern Slavonic populations

OBJECTIVE: To describe and compare the 3' apolipoprotein (Apo) B minisatellite allele frequency distributions of Eastern Slavonic populations and their Uralic, Altaic, and Caucasian speaking neighbors. METHODS: Healthy individuals of 10 populations among Russians, Byelorussians, Komis and Bashkirs were studied for variable number tandem repeats (VNTRs) in the 3'ApoB minisatellite region. Data were analyzed with other results reported for this polymorphism in eastern Europeans and Siberians. RESULTS: Allele frequency spectra in Eastern Slavonic, Northern Caucasian and Finno-Ugric speaking populations are bimodal with the main peak in alleles 34-36 and a secondary mode around allele 48, whereas Altaic speaking populations have a unimodal allele frequency distribution with a peak of around 34-36 VNTRs. Population relationships were revealed using both multidimensional scaling analysis (based on Nei's genetic distance estimate) and testing for genetic heterogeneity. Eastern Slavonic populations (Russians, Ukrainians, Byelorussians) were most closely related to each other and formed a separate tight clusterwhen plotted. Testing for genetic heterogeneity among the Eastern Slavonic ethnic groups revealed maximum diversity among Byelorussians, followed by Russians, then Ukrainians.The 3'ApoB minisatellite variability reveals little heterogeneityamong the Eastern Slavonic ethnic groups, whereas there wassignificant heterogeneity for Northern Caucasian and Altaic speakers. CONCLUSION: For this 3'ApoB polymorphism the Eastern Slavonic populations, despite their wide geographical distribution, appear to be much more homogenous than other ethnic groups of the region. Multidimensional scaling analysis of these data allowed for differentiation between individual populations from an ethnic group even if there is little heterogeneity.     

HindIII polymorphism of lipoprotein lipase gene and risk of myocardial infarction

The purpose of this study was to determine whether HindIII restriction polymorphism found in intron 8 of lipoprotein lipase gene is associated with the onset of myocardial infarction (MI) in Russians and Tartars living in Bashkortostan. HindIII polymorphism was investigated by the polymerase chain reaction in myocardial infarction survivors (males aged under 55 years (98 Russians and 68 Tartars) and in controls (53 Russians and 80 Tartars). The distribution of genotypes and allele frequencies in the controls were as follows: the frequencies of genotypes HindIII(-/-), HindIII(+/-), and HindIII(+/+) in Russians (3.77, 49.06, and 47.17%, respectively) did not differ from those in Tartars (7.50, 51.24, and 41.25%, respectively), while the frequency of HindIII(-) allele was 28.30% in Russians and 33.13% in Tartars. Among Tartars, the HindIII(+/+) genotype was more common in myocardial infarction survivors than in controls (OR 2.03). In the Russians this genotype was not associated with the risk of MI. The frequencies of HindIII(+/+) genotype and allele HindIII(+) were significantly higher (OR 8.96 and 6.71, respectively) and frequencies of HindIII(+/-) genotype and allele HindIII(-) were lower (OR 0.13 and 0.15) in Russian patients with repeated MI. These findings indicate that HindIII polymorphism may be a genetic risk factor for MI before 55 years of age in the Tartars and for repeated MI in Russians. This association prompts genotyping of HindIII polymorphism for predicting MI recurrence in Russian survivors after MI.     

Alpha-1-antitrypsin (PI) subtypes in Russians and Poles.

alpha-1-antitrypsin (PI) subtypes were studied in Poles and Russians. The frequencies of the PI alleles were similar in the two populations, with the exception of the Z allele, whose frequency was significantly lower in Poles. The M3 allele frequency, which is highly heterogeneous in European populations, has medium frequencies in Poles and Russians.     

Ecogenetic cause of polymorphism of transferrin (Tf) in various sex and age groups of Russians and Buryats

The distribution of transferrin (Tf) suballeles have been studied in Russians and Buriats, in connection with sex-age characters. No directional change in Tf suballele frequencies was obtained for age cohorts of Buriats. The tendency for decrease in the Tf allele frequency was noted in oldest age groups of Russians. The differences between Russians and Buriats were conditioned by differences between female subgroups, with respect to transferrins solely. The frequencies of relatively rare Tf alleles (C3, B, D) were higher in female subgroups, as compared with males.     

Analysis of insertion-deletion polymorphism in serotonin transporter gene in men of different ethnic appurtenance with acute alcoholic psychosis

Analysis of insertion-deletion polymorphism of serotonin vector gene (SLC6A4) was carried out in Russian and Tatar men with acute alcoholic psychosis. Significant interpopulation differences in the distribution of SLC6A4 genotype and allele frequencies were revealed. A relationship of L/S gene with the disease was detected in Russians and Tatars, but the presence of heterozygotic genotype was associated with early onset of chronic alcoholization and development of acute alcoholic psychosis in Tatars and with later alcoholization and disease development in Russians. The share of S/S genotype was significantly decreased in Russian patients aged over 35 years, which suggests selection aimed at elimination of short allele homozygotes among patients with this disease and probably different genetic prerequisites for early and late development of the disease in Russians. In Tatars aged over 35 years acute alcoholic psychosis is associated with L/L genotype (RR-3).     

Distribution of Gd- alleles in some ethnic groups of the USSR

Summary A population study of Gd^- allele distribution was made in similar (age-sex) samples of schoolchildren and students from different ethnic groups: Russians, Ashkenazi Jews, and Azerbaijanians. Both the frequency and the spectrum of the Gd^- alleles were quite different. The Gd^- frequency in Russians (Kostroma region) was 0.36%; in Ashkenazim (Gomel region), 0.91%; in Azerbaijanians (Sheki region and Apsheron region), 3.6% and 10.5%, respectively. G6PD deficiency in Russians is represented by familial forms; in Ashkenazi Jews by class II alleles Kirovograd and Zhitomir; and in Azerbaijanians, by a wide spectrum of class II and III alleles. Genetic factors involved in the formation of Gd^- allele frequencies and the spectrum in these three ethnic groups are discussed.     

Study of the most often encountered allele of the HLA-B27 gene in Tuvinian and Russian inhabitants of Western Siberia

HLA-B27 gene frequencies and allelic polymorphism were studied in two Siberian ethnic groups: Russians from Novosibirsk (western Siberia) and Tuvinians from Kyzyl (southern Siberia). The HLA-B27 frequencies were determined by means of serologic typing of HLA antigens in 198 Tuvinians and 288 Russians. Molecular typing was performed via hybridization of oligonucleotide probes with amplified DNAs obtained from 30 HLA-B27-positive Russians and 11 HLA-B27-positive Tuvinians. The HLA-B27 gene frequencies in Tuvinians and Russians were 5.5 and 10.4%, respectively. Molecular variants of the HLA-B27 gene were studied in Tuvinians for the first time. The proportions of the HLA-B2705 and HLA-B2704 alleles were found to be 64 and 36%, respectively, in the population studied. The presence of the HLA-B2704 allele indicates a Mongoloid origin of Tuvinians. In the Russian population of Novosibirsk, the HLA-B2704 allele was not found, whereas the proportions of the HLA-B2705 and HLA-B2702 alleles were 76.2 and 23.8%, respectively, which is characteristic of Caucasoid populations.     

Endothelial nitric oxide synthase gene minisatellite polymorphism: study in populations of the Volga-Ural region and analysis of associations with myocardial infarct and essential hypertension]

The 27-bp tandem repeat polymorphism in intron 4 of the endothelial nitric oxide synthase gene (eNOS) in populations of the Volga-Ural region was studied by means of polymerase chain reaction. In Russians and Tatars, the possible association of this polymorphism with coronary heart disease complicated by either myocaridal infarction or by essential hypertension was examined. Russians with essential hypertension associated with hypertrophy of the left ventricle displayed a statistically significant increase of the eNOS4A/B genotype and the A allele frequencies along with the decrease of the frequencies of the eNOS4B/B genotype and the B allele. In Tatars survived from myocardial infarction and with the risk of cardiovascular diseases (smoking or burdened heredity), a statistically significant increase of the frequencies of the eNOS4A/B genotype and the A allele was observed. Thus, in Russians the eNOS4A/B genotype was associated with the development of essential hypertension, while in Tatars it was associated with the risk of myocardial infarction.     

Comparative analysis of allele polymorphism of three short tandem repeats in the Russian, Uzbek and Georgian populations

The allele polymorphism of the AGC short tandem repeat (STR) of exon 1 of the androgen receptor (AR) gene located in Xq11-12, ATCT STR of intron 40 of the von Willebrand factor (vWF) gene located in chromosome 12p12, and AGAT STR of an anonymous DNA sequence (STRX1) from the short arm of the X chromosome was analyzed in the Georgian, Uzbek, and Russian populations. Polymerase chain reaction (PCR) with DNA of unrelated persons revealed 14 AR, 7 vWF, and 7 STRX1 alleles in Georgians; 14, 8, and 6 alleles, respectively, in Uzbeks; and 16, 8, and 9 alleles, respectively, in Russians. The heterozygosity at these STR was 0.61, 0.78, and 0.46 in Georgians; 0.60, 0.83, and 0.44 in Uzbeks; and 0.80, 0.70, and 0.58 in Russians. The correspondence of genotype frequencies to the Hardy-Weinberg equilibrium was observed with AR STR in Russians and Uzbeks, STRX1 STR in Georgians, and vWF in all three populations. A significant deviation from the equilibrium was found for STRX1 in Russians and Uzbeks and AR in Georgians. The potential of individualization was 0.05 for AR, 0.13 for vWF, and 0.18 for STRX1 in Georgians; 0.04, 0.09, and 0.13, respectively in Uzbeks; and 0.05, 0.14, and 0.07, respectively, in Russians. The allele and genotype frequency distributions of each STR were analyzed in all three populations. Allele frequencies in the populations were compared by the Kolmogorov-Smirnov test. The Russian population significantly differed in allele frequencies of the three STR from Uzbeks and in those of STRX1 and AR from Georgians. Georgians and Uzbeks significantly differed in vWF and STRX1 frequencies. The possibility of using the three STR in molecular diagnosis of the corresponding monogenic diseases, population genetic studies, and personal identification is discussed.     

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.     

Polymorphism A/G in position +49 of CTLA4 exon 1 in multiple sclerosis in Russians

The association of multiple sclerosis (MS) with alleles A and G of the cytotoxic T-lymphocyte antigen 4 (CTLA4) gene, a candidate gene for autoimmune disorders, was studied. The allele polymorphism results from single nucleotide substitution (A/G) in position +49 of exon 1 and leads to substitution Thr-->Ala in the leader peptide. The case-control study involved two groups of ethnic Russians: 168 MS patients and 209 healthy subjects from central Russia. Genotype frequencies were in agreement with the Hardy-Weinberg equilibrium in both groups (P > 0.05). The controls significantly differed in CTLA4 allele and genotype frequencies from Mongoloids but not from other Caucasians. No association was observed between MS and CTLA4. In addition, the combined association with MS was analyzed for both the CTLA4 alleles and allele groups of HLA DRB1. The results showed that the CTLA4 dimorphism does not affect susceptibility to MS in ethnic Russians, be these stratified or not with regard to DRB1 alleles corresponding to serologic specificities DR1 to DR16.     

Comparison CCR5de132 mutation in the CCR5 gene frequencies in Russians, Tuvinians, and in different groups of HIV-infected individuals

The 32-bp deletion (CCR5del32 mutation) in the CCR5 (chemokine (C-C motif) receptor 5) gene, encoding CCR5 chemokine receptor, is one of the factors determining natural resistance to human immunodeficiency virus (HIV-1) infection. In the present study, the samples of Russians (n = 107), Tuvinians (n = 50), and HIV-infected individuals were examined for the presence of CCR5del32 mutation in the CCR5 gene. The CCR5del32 allele frequency in Russians and Tuvinians constituted 7.84 and 2%, respectively. Among HIV-1 infected individuals, two groups, of macrophage-tropic HIV-1 strain- and T-cell-tropic HIV-1 strain-infected were distinguished. The CCR5del32 allele frequency in the first group (6.45%) was lower than in the second one (8.73%). Statistical treatment of the HIV-1 infected individuals typing data showed that the difference in the CCR5del32 allele frequencies between the groups of sexually (macrophage-tropic) and parenterally (T-cell-tropic) infected individuals observed was within the limit of random deviation.     

Polymorphism of alcohol dehydrogenase gene ADH1B in eastern Slavic and Iranian-speaking populations

Frequencies of alleles and genotypes for alcohol dehydrogenase gene ADH1B (arg47his polymorphism), associated with alcohol tolerance/sensitivity, were determined. It was demonstrated that the frequency of allele ADH1B*47his, corresponding to atypical alcohol dehydrogenase variant in Russians, Ukrainians, Iranians, and mountain-dwellers of the Pamirs constituted 3, 7, 24, and 22%, respectively. The frequencies established were consistent with the allele frequency distribution pattern among the populations of Eurasia. Russians and Ukrainians were indistinguishable from other European populations relative to the frequency of allele ADH1B*47his, and consequently, relative to specific features of ethanol metabolic pathways. The data obtained provide refinement of the geographic pattern of ADH1B*47his frequency distribution in Eurasia.     

Polymorphism of pigmentation genes (<Emphasis Type="Italic">OCA2</Emphasis> and <Emphasis Type="Italic">ASIP</Emphasis>) in some populations of Russia

In Russian populations, polymorphism of two pigmentation system genes, OCA2 (loci 305, 355, and 419, tested in Russians, Buryats, Chukchi, Koryaks, and Evens) and ASIP (locus 8818, tested in Russians and Buryats) was examined. Pairwise comparisons of the F _ST distances between the populations showed that only the populations from Northeast Asia (Chukchi, Koryaks, and Evens) were statistically significantly different from all other populations, at least relative to one of the OCA2 locus. In Russians from Pskov oblast and Novgorod oblast, increased frequency (up to 6%) of the OCA2 allele 419A was revealed. In earlier studies, as association of this allele with green eye color was demonstrated. The data obtained in terms of their application for ethnic population genetics.     

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 ?4, 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 ?3 allele in these populations ranged from less than 75 to 95%. The frequencies of alleles ?3 and ?4 were 0.714 and 0.205 in Saami, 0.735 and 0.220 in Komi-Izhemts, 0.770 and 0.130 in Komi-Zyryans, 0.771 and 0.149 in Udmurts, 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 ?3 and ?4 allele frequencies in the populations examined was comparable to the frequency distribution pattern of these alleles in other populations of Eurasia.     

Haplotypes of two diallelic Y chromosome loci in the indigenous and migrant populations of Siberia

Two diallelic Y-chromosome markers, the Y Alu polymorphism (YAP) and the T-C transition (Tat), were analyzed in the indigenous (Tuvinian, Buryat, Northern Altaic, and Tatar) and migrant (Slavic) populations of Siberia. A high frequency of the allele C was revealed in several indigenous populations (25-55%) and in Russians (20.8%). The YAP+ allele occurred at a surprisingly high frequency (31.4%) and was completely linked with the C allele in Buryats. The YAP+ chromosome was also found in the Tuvinian population (1.5%). The two diallelic loci showed a marked linkage disequilibrium (D = 92.4%) in the total sample. The YAP-/T and YAP-/C haplotypes prevailed in both indigenous and migrant populations: their respective frequencies were 80.4 and 19.6% in the Slavic population and 71.8 and 19.9%, respectively, in the indigenous one. The YAP+/C (7.8%) and YAP+/T (0.5%) haplotypes were found only in the indigenous population. An appreciable heterogeneity in haplotype frequency distribution between regional subpopulations was revealed in Russians, Tuvinians, and Buryats. The origin and evolution of Y-chromosome lines in Northern Asia are considered.