[Genetic predisposition to development of toxic liver cirrhosis caused by alcohol]. / Geneticheskaia predraspolozhennost' k razvitiiu toksicheskogo twirroza pecheni, obuslovlennogo deistviem alkogolia.

Comprehensive analysis of the contribution of genetic factors into predisposition to alcoholic toxic cirrhosis (TC) was performed. The ABO, RH, HP, TF, GC, PI, ACP1, PGM1, ESD, GLO1, and GST1 genetic polymorphisms were compared in 34- to 59-year-old male TC patients and control donors of the same sex and age. The phenotypic frequencies in the TC group deviated from the theoretically expected values; the main difference was the excess of rare homozygotes for the loci GC, ACP1, ESD, and GLO1. In the TC patients, the observed heterozygosity (Ho) was considerably lower than the theoretically expected value (H(e)). Wright's fixation index (F) in the TC patients was 30 times higher than in the control group (0.0888 and 0.0027, respectively). The frequencies of PI*Z and PI*S, the PI alleles that are responsible for lower concentrations of proteinase inhibitor, were 12 and 6 times higher in the TC than in the control group. The TC patients exhibited a significantly higher frequency of the liver glutathione-S-transferase GST1*0 allele, whereas the GST1*2 frequency was two times higher in the control subjects than in the TC patients (0.2522 and 0.0953, respectively). The TC and control groups showed statistically significant differences in the frequencies of the following alleles of six independent loci: ABO*0, TF*C1, TF*C2, PI*M1, PI*Z, ACP1*C, PGM1*1+, PGM1*1-, PGM1*2-, GST1*0, and GST1*2. The haptoglobin level was significantly higher and the serum transferrin level was drastically lower in all phenotypic groups of TC patients than in control subjects. The concentrations of IgM and IgG depended on the HP, GC, and PI phenotypes. The total and direct reacting bilirubin concentrations depended on the erythrocytic-enzyme phenotypes (ACP1, PGM1, and GLO1) in both TC and control groups.

[The Russian gene pool. Frequency of genetic markers]. / Russkii genofond. Chastoty geneticheskikh markerov.

Frequency distribution of several genetic markers was studied in ethnic Russians from the Moscow, Bryansk, Ryazan', Kostroma, Novgorod, Arkhangel'sk, and Sverdlovsk oblasts and Udmurtiya. Systems AB0, RH, HP, TF, GC, PI, C'3, ACP1, PGM1, ESD, GLO1, 6PGD, and AK were analyzed in most samples. New data on informative polymorphic genetic loci showed that the Russian gene pool mostly displays Caucasoid features. In addition, Y-chromosomal short tandem repeats (STRs) DYS19, DYS390, and YCAII were analyzed in the Russian samples. STRs of the chromosome are particularly valuable for elucidating ethnogenetic processes in Eastern Europe. Frequency distributions of the Y-chromosomal markers in Russians were intermediate between those of West European populations and eastern Finno-Ugric ethnoses of the Volga region. A marked longitudinal gradient was revealed for frequencies of several molecular markers.

[Differences in allele frequency at the BAIB locus, determining the level of expression of beta-aminoisobutyric acid, in healthy donors and coronary artery atherosclerosis patients from Buryat and Lithuanian populations]. / Razlichiia v chastotakh alleleiv lokuse BAIB, opredeliaiushchem uroven' i ékspretsii beta-aminoizomaslianoi kisloty, u zdorovykh donorov i bol'nykh aterosklerozom koronarnykh arterii iz buriatskoi i litovskoi populiatsii.

Phenotype and allele frequencies of the genetically dimorphic system determining urinary excretion of beta-aminoisobutyric acid (BAIB) were studied in population samples of Buryats from the Aginskii Buryat Autonomous District and Lithuanians from Vilnius and in patients with coronary atherosclerosis (CA) from both populations. Frequency of allele BAIB*b, which determines high BAIB excretion, proved to be more than twice higher in Buryats compared with the population sample of Lithuanians (0.620 versus 0.289, respectively). The proportion of individuals with high BAIB excretion in CA patients of either ethnic sample was twice higher than in the corresponding control sample. Frequency of allele BAIB*b in CA patients and healthy individuals was 0.348 and 0.242, respectively, in the Lithuanian population and 0.775 and 0.557, respectively, in the Buryat population. Thus, assessment of urinary excretion of BAIB proved to be prognostically valuable. The method used to detect a variation in BAIB excretion is relatively inexpensive, simple, and suitable for mass screening of patients and healthy individuals (population control). After additional testing with representative samples, the method can be used as an accessory diagnostic test in patients with cardiovascular disorders.

[Possible connection between the level of heterozygosity of biochemical gene markers in patients with lung diseases]. / Vozmozhnaia sviaz' mezhdu urovnem geterozigotnosti po biokhimicheskim markeram genov u bol'nykh s legochnoi patologiei.

The comparative heterozygosity level was estimated in patients suffering from squamous epithelial lung cancer (SELC) and in patients with chronic pneumonia with bronchiectases. To estimate heterozygosity, seven loci, reflecting normal diversity in human populations, were used (HP, TF, GC, PI, GL01, ACP1, PGM1). SELC patients with an uncomplicated postoperative period were distinguished by an increase in the level of observed heterozygosity (Hzero = 0.3916) in comparison with the theoretically expected value (H(e) = 0.4361). Patients having chronic pneumonia with bronchiectases with a complicated postoperative period were distinguished by an increase in the observed and expected level of heterozygosity (Hzero = 0.3737, H(e) = 0.3837) in comparison with that in the patient cohort with an uncomplicated postoperative period. The Wright's fixation index had a high value in the SELC cohort with an uncomplicated postoperative period (F = 0.1073) and a low value in patients with complicated cases (0.0048), witnessing the polar divergence of those patients from the total group of patients (0.0598) and the control (0.0388). The D criterion, reflecting deviation from the maximum heterozygosity level, distinguished the SELC patient cohort with a complicated postoperative period from patients with uncomplicated cases by the HP, GC, and ACP1 loci. The D criterion distinguished the SELC patients from the healthy control groups by the PGM1 locus.

[Effect of hereditary factors on tolerance for surgical treatment in patients with lung cancer]. / Vliianie nasledstvennykh faktorov na perenosimost' khirurgicheskikh operatsii u bol'nykh rakom legkogo.

Genetic polymorphism at 10 independent loci (ABO, RH, HP, GC, PI, TF, ACP1, PGM1, GLO1, and PTC) was studied in male patients with lung squamous cell carcinoma. These patients were divided into two groups, depending on their tolerance for surgical intervention and on the postoperative course: (1) patients with an uneventful postoperative period and (2) patients with postoperative complications. The genetic structure of the combined sample at the loci studied did not differ from that of the control group consisting of health people (population control). Genotypic differences might manifest at the postoperative stage rather than at the onset of the disease, and determine the presence of postoperative complications. However, comparative analysis of the two groups of patients revealed their polar divergence in respect to phenotype and gene frequencies at certain loci. Moreover, the genotypic structure of patients in both groups differed from that in the combined sample and in the population control. In the group with postoperative complications, higher frequencies of the alleles GC*1F, ACP1*A, and HP*2 were observed. By contrast, the group of patients with an uneventful postoperative period demonstrated prevalence of the alternative alleles of these loci: GC*2, ACP1*B, and HP*1. The greatest difference in the distribution of informative allele frequencies was observed between the group of patients with postoperative complications and the control group. This is evidence that these groups significantly differ in their genetic structure. Such divergence is largely determined by the polymorphic multifunctional systems of serum proteins.

[Ecogenetic aspects of the study of phenotypes and levels of beta-aminoisobutyric acid excretion]. / Ekogeneticheskie aspekty izucheniia fenotipov i urovnei ékskretsii beta-aminoizomaslianoi kisloty.

The levels of excretion of beta-aminoisobutyric acid (BAIB) in urea were examined in five groups. The distribution of BAIB concentration revealed the existence of high and low excretors in each group. Asbestosis patients had the lowest frequency of high excretors. The BAIB concentration among high excretors was similar for all the groups. The BAIB levels of low excretors varied. The most alike were two children groups, asbestosis patients and the workers from the town Asbest.

[Genetic polymorphism of haptoglobin and quantitative changes in its levels during exposure to asbestos]. / Geneticheskii polimorfizm gaptoglobina i kolichestvennye izmeneniia v ego soderzhanii pri vozdeistvii asbesta.

The polymorphism and serum levels of haptoglobin were studied in asbestosis patients, in the control and the workers exposed to asbest. Hp1-1 has the highest, Hp2-2--the lowest and Hp2-1 has the intermediate concentration of this protein. In the course of contact with asbest, and especially in asbestosis patients, the haptoglobin levels are higher (for all phenotypes). The standard deviation from the Hp concentration in asbestosis patients was significantly higher. The phenotypes Hp1-1 were found more often in asbestosis patients than among asbest-exposed workers.

[The association of genetic and functional variability of alpha 1-antitrypsin in asbestosis]. / Sopriazhennost' geneticheskoi i funktsional'noi izmenchivosti alpha 1-antitripsina pri asbestoze.

The polymorphism and serum levels of alpha 1-antitrypsin (AT) were studied in asbestosis patients, the control and the workers exposed to mineral flax longer or less than ten years. M1S, M3S, M1Z and M2M2 phenotypes had low concentration of this protein. In the course of contact with mineral flax decrease in alpha 1-AT concentration was found. The phenotypes with low protein levels were very rare among workers contacting with asbestos for a long time, and one of them--M1S was more often encountered in asbestosis patients. The standard deviation from the alpha 1-AT concentration was significantly higher in asbestosis patients.

[Gene manifestations in negative man-made environment: a selective genetically determined sensitivity to asbestos]. / Proiavlenie genov v usloviiakh negativnoi antropogennoi sredy: izbiratel'naia geneticheski obuslovlennaia chuvstvitel'nost' k asbestu.

Genetic polymorphism of the systems of haptoglobin, transferrin, alpha 1-antitrypsin and complement C3 was investigated in patients with asbestosis and in healthy individuals who contacted with asbestos for a long time. The significant differences were discovered between the groups under comparison in the distribution of the phenotypic and genic frequencies in these loci. Simultaneous studies of the levels of these proteins depending on the phenotype demonstrated differentiation of the patients and healthy subjects according to the mean values and dispersions. The data obtained provide evidence in favour of occupational selection as regards the genetic factors investigated.

[Hereditary polymorphism of glutathione-S-transferase in the human liver in normal conditions and in alcoholic hepatitis]. / Nasledstvennyi polimorfizm glutation-S-transferazy pecheni cheloveka v norme i pri alkogol'nom gepatite.

A total of 100 autopsy liver extracts from Russian individuals were examined for glutathione-S-transferase I (GST1) isozymes by means of starch gel electrophoresis. The gene frequencies of GST1* 1, GST1* 2 and GST1* 0 were 0.051, 0.251 and 0.697, respectively. Analysis of data obtained and those in literature for other populations revealed the difference between European and Mongoloid groups. The GST1 0 phenotype was found in samples of liver from individuals with alcoholic hepatitis at frequency 77.3%. The gene frequencies for GST1* 1, GST1* 2 and GST1* 0 were 0.020, 0.100 and 0.879, respectively.

[Genetic geography of inherited dimorphism of ear wax by its consistency]. / Genogeografiia nasledstvennogo dimorfizma ushnoi sery po ee konsistentsii.

Data on cerumen types were collected in three population groups of Pamir mountain region. The observed frequencies of dominant w and recessive d alleles which determine wet and dry types of ear wax are equal, accordingly: in Khuf population (Western Pamir) to 0.6603 and 0.3397; in Pastkhuff population (Western Pamir) to 0.6078 and 0.3922; in Kirghizes of Central Pamir to 0.3606 and 0.6394. We present data on cerumen types in 23 populations of the USSR also. The world information on distribution cerumen types was summed up (over 80 populations). No connection of gene frequencies of cerumen with natural abiotic factors of environment was revealed. Strong correlation of the genes described with mongoloid peculiarities was established: epicanthus r = 0.718, the haplotype Gmz, a, b, 0, 3, 5, s, t (Gm(1, 11, 13, 15, 16) r = 0.522.