[Genetic aspects of digestive diseases. Part 1].

The paper presents the data available in the literature on mutations in known genes in pancreatitis, such as cationic trypsinogen (PRSS1), pancreatic secretory trypsin inhibitor (PSTI/SPINK1), cystic fibrosis (CFTR), and apolipoprotein E (APOE) genes, as well as the new candidate gene--chymotrypsinogen (CTRC). It also gives the results of the authors studies estimating the spread of the mutations in the PRSS1 (2.5%), PSTI/SPINK1 (3.3%), and CFTR (0.8%) genes, as well as APOE polymorphism in patients with pancreatitis. It is shown that the E4 allele of the APOE gene was more frequently identified in patients with acute pancreatitis than in those with chronic pancreatitis (0.143 +/- 0.05 and 0.026 +/- 0.02, respectively; p < 0.05). An overview is given of 7 major classes of candidate genes implicated in the pathogenesis of cholesterol cholelithiasis (CL): hepatic enzymes regulating blood lipid composition; receptors of lipoproteins, hepatic and intestinal membrane and intracellular transport proteins; factors regulating the transcription of lipids and bile salts, cholecystokinin and its receptors, and mucin. In the authors' epidemiological study, the spread of APOE alleles and genotypes did not differ in women with and without CL; low molecular-weight apolipoprotein(a) isoforms (B, S2) were significantly found in patients with CL than in those without CL; the spread of the CG genotype in the TRPM8 gene was significantly lower in women with cholesterol CL than that in the Novosibirsk population. These polymorphisms have been proved to be associated with bile cholesterol concentrations in women with cholesterol CL. The opposite effect of the APOE4 allele on gallbladder stone formation processes is demonstrated, by using the APOE polymorphism as an example, which shows it necessary to examine each specific population to elicit a possible association between the polymorphism of different genes and gastrointestinal tract diseases.

[Gastrointestinal symptoms in adult population of Novosibirsk city: prevalence and risk factors].

AIM: To study prevalence of dyspepsia symptoms, gastroesophageal reflux (GER) and irritable bowel syndrome (ICS) in city population and to detect relevant risk factors. MATERIAL AND METHODS: Gastrointestinal symptoms were investigated with a validated questionnaire Bowel Disease Questionnaire and dyspepsia, GER, ICS syndromes were identified in a representative sample of adult Novosibirsk population (1040 patients, 492 males and 548 females aged 45-69 years). Risk factors were studied by social-demographic and antropometric parameters, smoking, drinking and administration of nonsteroidal anti-inflammatory drugs (NSAD). Depression was assessed by CESD questionnaire. Helicobacter pylori infection and the level of pepsinogen I were studied with enzyme immunoassay Biohit GastroPanel (Biohit, Finland). RESULTS: Incidence of dyspepsia was 38%, GER--30%, ICS--19%. One of the illnesses was found in 56% cases, combination of the conditions--in 24%. Females had dyspepsia and ICS much more frequently. Social-demographic parameters (age, marital status, education, labor activity), alcohol consumption, intake of NSAD, Helicobacter pylori infection had no significant effect on the incidence of gastrointestinal symptoms. GER occurred more frequently in smoking males. Overweight was characteristic both for GER males and females. Severe depression was associated with the risk of dyspepsia and ICS both in females and males. Hyperpepsinogenemia increased the rate of GER detection in males and dyspepsia in females. CONCLUSION: Dyspepsia, GER and ICS were seen in 50% adult population and often combine, but the risk factors differ. Some of the latter can be modified and prevented.

[Gamma-glytamiltransferase activity and cardiovascular diseases (ischemic heart disease and cerebral stroke)].

PURPOSE: To investigate association between gamma-glytamiltransferase levels and the development of CVD. The data were taken from materials of the epidemiological study " Determinants of cardiovascular disease in Eastern Europe " , the HAPPIE project. We investigated representative samples from non-organized population of men and women 45 - 69 years old living in Novosibirsk - 9361 subjects (4275 men and 5086 women). The program of study included: questionnaire of previous CVD, smoking status and alcohol consumption; two blood pressure measurements; anthropometry, biochemical analysis (gamma-glytamiltransferase, total cholesterol, HDL cholesterol, and triglycerides) and rest ECG. Among all subjects we distinguished three groups: first - patients with diagnosed ischemic heart disease (angina pectoris or myocardial infarction) and without previous cerebral stroke; second - patients with previous cerebral stroke (without ischemic heart disease); third - patients without previous ischemic heart disease and cerebral stroke (control group). We revealed reliable data on sex-dependent difference of gamma-glytamiltransferase activity: men have higher gamma-glytamiltransferase activity compared with women in all age groups. Subjects who didn t take alcoholic drinks during the last year have noticeably lower gamma-glytamiltransferase level than those who took alcoholic drinks during that period. Gamma-glytamiltransferase activity was higher both in men and women in group with ischemic heart disease, than in control group. We did not reveal difference in gamma-glytamiltransferase activity between groups with cerebral stroke and control group. The similar patterns were revealed in subjects who didn't take alcoholic drinks during the last year.

[Hyperhomocysteinemia in men of Novosibirsk].

Prevalence of hyperhomocysteinemia (HHC) in a sample of male population (n=84, age 50-64 year) of Novosibirsk assessed in the framework of the international project "Determinants of cardio-vascular diseases in the Eastern Europe: multicentral cohort research" during winter-spring period of vitamin deficiency was 50%. In 90.5% of cases HHC was moderate (15-30 micromol/l) and in 9.5% of cases -- medium (30-100 micromol/l). No correlations or independent associations were found between homocysteine blood level and CHD, as well as main risk factors (hyperlipidemia, hypertension, smoking and excessive body weight). No cases of CHD were registered among men with medium HHC. Homocysteinemia correlated positively with age, history of stroke, and negatively -- with alpha-tocopherol concentration in LDL. Men with medium HHC compared with those with normohomocysteinemia had higher systolic and diastolic blood pressure and 29% lower alpha-tocopherol concentration in LDL.

[Oxidized low density lipoproteins and their association with some atherosclerosis risk factors in a population of Novosibirsk men].

Lipid peroxidation products (LPP) and liposoluble antioxidants in low density lipoproteins (LDL), resistance of LDL to oxidation were determined in 305 male inhabitants of Novosibirsk aged 30-70 years. Other methods of examination included questionnaires, anthropometry, registration of blood pressure (BP) and ECG, measurement of total cholesterol (TCH), high density lipoprotein cholesterol (HDLCH), triglycerides (TG). Ten and 90% cut points of percentile distribution of LPP in LDL and parameters of their resistance to oxidation in male population of Novosibirsk were used as regional reference values. Interrelationships were found between LPP in LDL, parameters of LDL resistance to oxidation, levels of antioxidants in LDL, and TCH, TG, HDL CH, smoking, BP and body mass index. Associations between LPP in LDL, LDL resistance to oxidation and TCH, HDLCH, TG, smoking and systolic BP were independent.

[Deletional polymorphism of the 11th intron of the human c-fms gene: allele frequency in certain Russian populations and possible functional significance]. / Deletsionnyi polimorfizm 11-go introna gena c-fms cheloveka: chastoty allelei v nekotorykh populiatsiiakh Rossii i vozmozhnaia funktsional'naia znachimost'.

Analysis of deletion polymorphism of human c-fms gene intron 11 (approximately 425-bp deletion) is of particular interest because of the increased proportion of the deletion heterozygotes among the infants born from the parents, one of which lacks the deletion allele, and the other is heterozygous for the deletion. In this study, allele and haplotype frequencies of the polymorphism examined were assessed in a number of Caucasoid and Mongoloid populations of Russia. In all populations tested, relatively high prevalence of the deletion-bearing allele, ranging from 9.45% in ethnic Germans to 20.75% in Altaians, was detected. Russians and Kazakhs were characterized by intermediate frequencies of the rare allele, constituting in these populations 12.89 and 14.93%, respectively. Hardy-Weinberg expectations were met in all populations examined, pointing to a stable level of polymorphism at the c-fms intron 11. It was established by the context analysis of DNA of the deleted fragment along with the flanking sequences that this region contained a number of transcription factor motifs (Ets, SRF, and Myc), potentially capable of the regulation of the M-CFF-dependant c-fms transcription. The deletion breakpoint was localized within the CArG motif, which, together with the neighboring ets motif, form the potential CArG/ets composite element. It was suggested that allele lacking the fragment of intron 11 could be restricted in its ability to modulate the level of the c-fms transcription in response to the action of M-CSF. The data of molecular epidemiological survey serve as the indirect evidence favoring the suggestion on the possible functional value of this gene fragment. It was demonstrated that in the samples of acute bronchitis and trichomoniasis patients allelic and genotype frequencies were statistically significantly different from those in the population sample. In case of trichmoniasis, the frequency of rare allele was 2.4 times lower, and in case of acute bronchitis it was 2.1 times higher than in the control sample.

[Prognostic value of duration and variability of QT and RR intervals in general population of Novosibirsk]. / Prognosticheskoe znachenie dlitel'nosti i variabel'nosti intervalov Q-T i R-R v obshchei populiatsii Novosibirska.

Increased duration and dispersion of QT interval and lowered variability of RR interval are considered to be probable precursors of dangerous ventricular arrhythmias and sudden death. Standard epidemiological methods were used for the study of a representative sample of nonorganized male population (age 25-64 years) in Novosibirsk in a framework of the MONICA project. Database of the total mortality register was used for verification of deaths. Resting ECGs were analyzed using the Minnesota code criteria blindly relative to other data of the study. Duration and dispersion of QT and QTc intervals as well as temporal parameters of RR variability were determined manually. Assessment of significance of these factors for prognosis was made with the use of methods of survival analysis. Among all characteristics of QTc interval maximal duration and dispersion of QTc were the strongest predictors of death from any cause and cardiovascular death being independent of age, mean blood pressure, ischemic heart disease, body mass index and smoking. Predictive power of these QTc interval parameters was similar in total male population and in subpopulation of patients with cardiovascular diseases. In men without cardiovascular diseases parameters of RR variability on ECG at rest were predictors of cardiovascular death independent of age, mean blood pressure, body mass index, total cholesterol and smoking.

[Relationship between various clinical parameters and duration and variability of Q-T and R-R intervals in ECG (an epidemiological population study)]. / Sviaz' nekotorykh klinicheskikh pokazatelei s parametrami dlitel'nosti i variabel'nosti intervalov Q-T i R-R na EKG (po materialam épidemiologicheskogo populiatsionnogo issledovaniia).

AIM: To study the relationship between clinical values of a standard epidemiological study of a male population and the length and variability of Q-T and R-R intervals. MATERIAL AND METHODS: A representative sampling from a male population (2184 subjects aged 25-64 years) in Novosibirsk was examined using standard epidemiological methods. Later 251 men were excluded from the study because of impossibility of correct analysis of ECG. The length and dispersion of Q-T interval and time parameters of variability of R-R interval were evaluated. RESULTS: The size and variability of Q-T and R-R intervals are associated with age and AP irrespective of other clinical parameters of a simultaneous epidemiological study. The length of R-R interval is independently related to body weight index, tobacco smoking, and plasma triglyceride level. R-R variability parameters are associated with coronary disease irrespective of the risk factors. CONCLUSION: Scanning studies with complex analysis of Q-T and R-R interval duration and variability effectively detect subjects at a high risk of arrhythmias and fatal events.

[Prevalence of and risk factors for gallstones in female population of Novosibirsk]. / Rasprostranennost' i faktory riksa razvitiia zhelchnokamennoi bolezni v zhenskoi populiatsii Novosibirska.

AIM: To investigate the prevalence of gallstones and associated factors in female population of Novosibirsk (Western Siberia). MATERIALS AND METHODS: A representative sample of 870 women aged 25-64 years was drawn from general population according to WHO "MONICA" protocol. The subjects were screened for the presence of gallstones by gallbladder ultrasonography, completed a questionnaire relating to food and alcohol consumption, smoking, gastrointestinal symptoms and obstetric history. They also underwent physical examination and blood chemistry tests. Age-adjusted prevalence of cholelithiasis was 9.5%. Increasing age, obesity, diabetes mellitus, consumption of animal fat, pregnancies and opisthorchiasis positively correlated with gallstones in univariate analysis. Serum lipids, family history of gallstones, consumption of alcohol and tobacco were not predictors of gallstones. Only association with age and obesity was significant in multivariate analysis. Among subjects with cholelithiasis 52.1% were not aware of having gallstones. Subjects with gallstones more frequently suffered from biliary colics and non-specific dyspeptic symptoms. However, their predictive value was poor. Cholecystectomized patients revealed more often upper abdominal pain and dyspeptic symptoms. CONCLUSION: Prevalence and risk factors for gallstones in female population of Novosibirsk are similar to those reported in Western European countries. Cholecystectomy is not recommended in patients with symptomless disease.

[Comparison of the results of provocation electrocardiographic tests with the questionnaire for detection of exertion-induced stenocardia (data of the epidemiological study)]. / Sopostavlenie rezul'tatov provokatsionnykh elektrokardiograficheskikh prob s dannymi oprosnika na vyiavlenie stenokardii napriazheniia (po materialam épidemiologicheskogo issledovaniia).

The results of a combination of functional electrocardiographic tests were compared with those of a WHO questionnaire for angina of effort. Coronary disease was verified in 37% of patients with a double diagnosis of angina of effort, and in 100% of cases of angina of effort combined with ischemic electrocardiographic changes.

[Cholesterol esterase activity of blood monocytes and the main risk factors of ischemic heart disease in men aged 20-59]. / Aktivnost' kholesterolésterazy monotitov krovi i osnovnye faktory riska ishemicheskoi bolezni serdtsa u muzhchin 20-59 let.

Changes in the activity of blood monocytic cholesterol esterase in men with major CHD risk factors (dyslipoproteinemia, arterial hypertension, excessive body mass) were described. Standard methods of epidemiological survey and a radionuclide method to determine cholesterol esterase activity applied to a representative sampling (195 persons) have shown that enzymatic activity was growing with age. In examinees with hyperlipoproteinemia of type IIa and IIb the activity of cholesterol esterase was decreased, and in persons with excessive body mass it was increased. In combination of 2-3 CHD risk factors significant differences in enzymatic activity were undetectable.

[Detection of long Q-T interval in mass screening of the population]. / Vyiavlenie udlinennogo intervala Q-T pri populiatsionnom issledovanii.

The incidence of lengthened Q-T interval in an open population of 45- to 54-year-old males was assessed in a random representative sample. Lengthened electrocardiographic Q-T interval was detected in 3.5% of cases. The identification of individuals with lengthened Q-T intervals at population screenings, their follow-up and the development of preventive measures against ventricular tachyarrhythmias and sudden death are shown to be warranted.