[Evaluation of association between 9 genetic polymorphism and myocardial infarction in the Siberian population].

AIM: to evaluate association between genetic polymorphism (SNPs) and myocardial infarction (identified in recent GWAS) as markers of high risk of myocardial infarction (MI) in Siberian population. Patients were divided into 2 groups - MI patients and control group (ratio 1:2) and presented the sapmle of population of Novosibirsk (9400 patients, 45-69 years) within international project HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe). 200 patients with MI (129 men, 71 women) were included. Control group - individuals without MI (420) matched for age and sex. Genomic DNA was extracted from venous blood by phenol-chloroform extraction. Gene polymorphism of genes tested by real-time PCR according to protocol (probes TaqMan, Applied Biosystems, USA) with the use of ABI 7900HT. The following SNPs were studied: rs28711149, rs499818, rs619203, rs10757278 and rs1333049 (hr. 9), rs1376251, rs2549513, rs4804611, rs17465637. The association of SNP and MI was confirmed for 4 of 9 studied SNPs: rs1333049 (hr. 9), rs10757278 (hr. 9), rs499818 (hr. 6), rs619203 gene ROS1. Heart rate was associated with rs1333049 and rs10757278. Glucose level was associated with rs619203, rs28711149 and rs1376251. Total cholesterol and atherogenic index was associated with rs28711149. For the first time in Russian population the associations of GWAS with myocardial infarction SNPs was detected for rs619203, rs499818, rs1333049 and rs10757278. These genetic markers can be used for assessing the risk of myocardial infarction in Russian population.

[24-Hour arterial pressure variability and 24-hour variability of pulse carries unidirectional character and is not associated with left ventricular hypertrophy (results of population study)].

Alternative prognostic interpretation of variability of arterial pressure (AP) and pulse seems contradictory if one considers classical conceptions of close physiological connection between AP and pulse. It is logical to expect that elevated variability of AP should be associated with elevated variability of pulse and vice versa. Within framework of the project EPOCH we examined a populational sample of inhabitants of Novosibirsk (129 men and 170 women) formed according to the family principle. Ambulatory 24-hour registration of AP and pulse was carried out with 15-30 minutes interval. Variability of AP turned out to be unidirectionally interconnected with variability of pulse and was not an independent marker of hypertrophy of the left ventricle but was associated with it at the account of concealed dependence on mean 24-hour AP. Cornell voltage index in persons with normal AP, "white coat" arterial hypertension (AH), "masked" AH was comparable and significantly lower than in subjects with sustained AH.

[Role of hyperlipidemia in cholelithiasis].

THE PURPOSE OF THE REVIEW: Was analyzed basic data on the contribution of blood serum lipids in the development of gallstone disease (GSD) in the world as well as in northern Russia, as well as the association of cholelithiasis and coronary heart disease (CHD). RECENT LITERATURE DATA: Worldwide, there is suffer from cholelithiasis 10 to 15% of the population. In Russia, about 60% of adults have a lipid metabolism. According to some epidemiological and clinical studies, serum lipid profile did not differ in patients with and without gallstone disease, in others with cholelithiasis observed hyperlipidemia. In an epidemiological study in the unorganized population of Novosibirsk cholelithiasis occurs more frequently among men and women with lipid disorders. Indigenous peoples of the North Asian Russia this disease is less common than among the aliens, which was accompanied by a more moderate hyperlipidemia. There was a positive association between gallstone disease and coronary heart disease. Despite the fact that hypertriglyceridemia and hypo by a majority of authors are recognized risk factors for gallstone disease, a consensus on the contribution of blood serum lipids in the pathogenesis of gallstone no. Since gallstone mostly composed of cholesterol, probably need to examine the level of serum lipids in a moment of gallstones after this time can be obscured link hyperlipidemia and holelitgenesis.

[Quality of life at dyspepsia and irritable bowel syndrome: population-based studies].

The aims of the study were to examine the prevalence of dyspepsia and irritable bowel syndrome (IBS) in the unselected population and to assess the quality of life (QOL) in these syndromes and their combination. The study involved 1,040 people, representing a random sample of adults aged 45-70 years (492 men, 548 women). To identify gastrointestinal symptoms using validated questionnaire, dyspepsia and IBS were diagnosed by Rome I criteria. QOL was assessed using a questionnaire SF-36. Dyspepsia was reported by 37.5% (30.1% men and 44.2% women, p < 0.001). The prevalence of IBS was 18.8% (12.0% men and 25,0% in women, p < 0.001). The combination of dyspepsia and IBS was noted in 12.0% (6.5% in men and 17.0% in women). Both dyspepsia and IBS cause significant decrease in QOL on most scales of the questionnaire SF-36 compared with those without these disorders. Their combination reduced QOL even more in comparison with isolated dyspepsia or IBS. Finally, high prevalence of dyspepsia and IBS was stated among the population, both conditions more frequently observed in women. QOL is significantly reduced in subjects with dyspepsia and IBS, especially if these syndromes combine.

[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.

[Sudden cardiac death and polymorphism of genes-candidates of cardiovascular diseases].

Aim of the study was to elucidate genetic markers associated with elevated risk of sudden cardiac death (SCD). We collected autopsy material during 1999 - 2001 in a process of forensic medical pathologo-anatomical examination of corpses of 182 men who had died suddenly in Octyabrsky district of Novosibirsk in the age of 25 - 64 years (mean age 53,6 +/- 7,9 years). We studied polymorphisms of the following genes: angiotensin converting enzyme - , glycoprotein IIb/IIIa - GPIIb/IIIa, alpha2b adrenoreceptor - ADRA2B, beta(1)-adrenoreceptor - ADRB1. Control comprised samples of population of men aged 25 - 35 and 55 - 64 years from the same district of Novosibirsk examined within framework of international WHO project MONICA. Comparison of frequencies of genotypes of polymorphism A1/A2 of GPIIb/IIIa gene in combined sample of population and group with SCD revealed in SCD group lowering of portion of A2/A2 homozygotes (5.0 and 1.2%, respectively, =0.029) and elevation of portion of A1/A2 heterozygotes (18.7 and 28.3%, respectively, =0.027). Odds ratio for a heterozygote to enter SCD group was 1.71 (95% confidence interval 1.0 to 2.77). Comparison of frequencies of genotypes and alleles of polymorphism A145G of ADRB1 gene in combined sample of population and group with SCD did not reveal any difference. Comparison of frequencies of polymorphism I/D of ACE gene in combined sample of population and group with SCD revealed significant lowering of frequencies of genotype I/I in SCD group (22.0 and 13.8%, respectively, p=0.033). There were no significant differences between SCD group and control in frequencies of studied polymorphism of alpha2b-adrenoreceptor gene.

[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.

[Providing of adult population of Novosibirsk with iodine].

32,7% of the population of Novosibirsk consume iodine salt. The median of iodine is revealed 106,8 mkg/l. The iodine deficiency is revealed 46,3%. It is not received an authentic difference in volumes of thyroid gland and parameters of TSH at surveyed with normal parameters of excretion of iodine in urine and at a various degree of expressiveness of iodine deficiency (p>0,05). Structural pathology of thyroid gland equally frequently meets at people with iodine deficiency and without iodine deficiency (p>0,05).

[Symptoms of gastroesophageal reflux and quality of life: population study].

AIM: To study prevalence of symptoms of gastroesophageal reflux (GER) in a free living population and to evaluate quality of life (QOL) in this disease. MATERIAL AND METHODS: The gastroenterological symptoms and QOL were studied in a representative sample of adult population of 495 males and 548 females aged 45-70 years using a validated questionnaire, SF-36 questionnaire. RESULTS: GER symptoms were seen in 17.0% responders, with the same frequency in men and women, in responders of different age. QOL was worse in responders with GER by 2 scales of SF-36 questionnaire: in males--"general well-being" and "viability", in females--"general well-being" and "physical functioning". In persons who had visited a doctor QOL was lower by all 8 scales than in those who had GER symptoms but had not visited a doctor. GER prevalence in Russia is similar to that in the West Europe and USA. QOL in GER patients is not low but worse in those who seek medical advice.

[The frequency of some infections in patients with coronary artery disease].

The paper is dedicated to associations between infective agents and coronary artery disease (CAD). The study design included examination of a random sample of non-organized population (389 adults aged 25 to 64 years). Using immune-enzyme assay, IgM and IgG antibodies to seven infective and parasite agents (Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Trichomonas vaginalis, Candida albicans, Opisthorchis felineus, and Giardia lamblia), as well as the level of IgE were measured. In patients with CAD, IgE level was significantly higher vs. controls, but is was not connected with the infections under study except opisthorchosis invasion. The incidence of some pathogens was higher in CAD patients vs. controls. The total number of infections detected in an individual was associated with a higher frequency of CAD and some atherosclerotic risk factors.

[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.

[10-year trends in body weight in men and women in Novosibirsk (1985-1995)].

AIM: To assess 10-year trends in prevalence of overweight and obesity in Novosibirsk population. MATERIAL AND METHODS: The data of three population surveys (a total of 9714 men and women aged 25-64 years) carried out according to WHO MONICA program. RESULTS: Obesity prevalence among males in 1985-1989 tended to a small rise without changes during subsequent 5 years. In females the prevalence of obesity and overweight decreased in 1985-1994. CONCLUSION: 10-year trends in prevalence of overweight and obesity were insignificant in men and beneficial in women of Novosibirsk population while the frequency of increased body mass in women remains relatively high.

[Significance of different methods in evaluation of prevalence of cholelithiasis in population: pathoanatomical and lifetime ultrasonic diagnostics]. / Znachenie razlichnykh metodov otsenki rasprostranennosti zhelchno-kamennoi bolezni v populiatsii: patologo-anatomicheskaia i prizhiznennaia ul'trazvukovaia diagnostika.

AIM: To evaluate the occurrence of cholelithiasis (CL) diagnosed by routine autopsy and to compare these data with the results of ultrasonographic examination of the general population. MATERIAL AND METHODS: Autopsy protocols (n = 1124) from a large general hospital were analysed, and a representative sample of Novosibirsk population (1678 examinees aged 25-64 years) was examined by ultrasonography. RESULTS: Prevalence of CL increased with age and was five-fold higher in females than in males. Both methods showed good concordance. The age-adjusted CL prevalence rates in 25-64 year-old groups was 1.94% in males and 9.53% in females in autopsy series, and 2.16% and 11.16%, respectively, in ultrasonographic study. CONCLUSION: Routine autopsy may serve as a reliable tool in evaluating prevalence of CL among the population provided the values are gender- and age-standardized.

[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.

[Prevalence of Helicobacter pylori CagA-producing strains within families]. / Rasprostranennost' CagA-produtsiruiushchikh shtammov Helicobacter pylori v sem'iakh.

During prophylactic examination of blood sera taken from the members of 59 families by the enzyme immunoassay, antibodies to H. pylori and CagA protein were determined. As shown in this study, the children of non-infected mothers proved to be infected in 6.3% of cases and the children of infected mothers, in 72.1% of cases (p < 0.001). The children of non-infected fathers were H. pylori-positive in 71.4% and those of infected fathers, in 58.4% of cases. The CagA status was found to coincide in mothers and their children (p = 0.01), but not in fathers and their children. These data indicate that children acquire H. pylori infection from the members of their family, mainly from their mothers.

[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.