Association of the APOE Gene Polymorphism with Depression in White Adults in the WHO "MONICA-Psychosocial" Program.

The APOE gene polymorphism is associated with the risk of the development of several neurological disorders. The aim of the study was to investigate the association of the APOE gene polymorphism with depression in the white adult population aged 25-64 years in Novosibirsk (Western Siberia). The third screening of the WHO program "MONICA-psychosocial" was conducted in 1994-1995. In total, 403 men (the average age was 34 ± 0.4 years, the response was 71%) and 531 women (the average age was 35 ± 0.4 years, the response was 72%) of the open population of residents aged 25-64 years of the Oktyabrsky district of Novosibirsk were examined. The "MONICA-MOPSY" psychosocial questionnaire was used to assess depression. A high level of depression was found in 12.8% of the population: in 8.9% of men and in 15.8% of women. The frequencies of APOE gene polymorphism genotypes ε2/3, ε2/4, ε3/3, ε3/4, and ε4/4 were 14.9%, 3.1%, 61.6%, 17.5%, and 2.9%, respectively. Carrying the ε3/4 genotype of the APOE gene increased the odds of developing major depression by 2.167 times (95% CI 1.100-4.266) compared to carrying the ε3/3 genotype of the APOE gene in people without depression (χ2 = 5.120 df = 1 p = 0.024). Carriers of the ε4 allele were 2.089 times (95% CI 1.160-3.761) more likely to have a high level of depression than those without this allele and no depression (χ2 = 6.148 df = 1 p = 0.013), and 2.049 times (95% CI 1.117-3.758) more likely to have a moderate level of depression than those without this allele (χ2 = 5.470 df = 1 p < 0.019). The ε4 allele of the APOE gene is associated with a high level of depression.

Association of Common Variants of APOE, CETP, and the 9p21.3 Chromosomal Region with the Risk of Myocardial Infarction: A Prospective Study.

The individual risk of an unfavorable cardiovascular outcome is determined by genetic factors in addition to lifestyle factors. This study was aimed at analyzing possible associations of several genetic factors with the risk of myocardial infarction (MI). For our study, we selected genes that have been significantly associated with MI in meta-analyses: the chromosomal region 9p21.3, the CETP gene, and the APOE gene. In total, 2286 randomly selected patients were included. Rs708272 and rs429358 and rs7412 were analyzed using RT-PCR via the TaqMan principle, and rs1333049 vas analyzed via a commercial KASP assay. In our sample, the frequencies of alleles and genotypes were consistent with frequencies in comparable populations of Eastern and Western Europe. Allele C of rs1333049 was significantly associated with MI among males (p = 0.027) and in the whole study sample (p = 0.008). We also revealed a significant association of the ɛ2/ɛ4 genotype of APOE with MI among males (p < 0.0001) and in the whole study sample (p < 0.0001). Thus, among the tested polymorphisms, some genotypes of rs1333049 and rs429358 and rs7412 are the most strongly associated with MI and can be recommended for inclusion into a genetic risk score.

Associations of APOE Gene Variants rs429358 and rs7412 with Parameters of the Blood Lipid Profile and the Risk of Myocardial Infarction and Death in a White Population of Western Siberia.

The present study aimed to analyze possible associations of rs7412 and rs429358 of the APOE gene with lipid profile parameters, the risk of myocardial infarction, and death in the mostly white population of Western Siberia (Russia). The study population was selected from a sample surveyed within the framework of the Health, Alcohol and Psychosocial Factors In Eastern Europe (HAPIEE) study (9360 subjects, age 53.8 ± 7.0 years, males/females 50/50). PCR was conducted with fluorescence detection according to the TaqMan principle on a real-time PCR machine. The frequency of a minor allele (C) of rs429358 was 0.13, and the frequency of a minor allele (T) of rs7412 was 0.09. In our study, the woman with the rare ɛ1/ɛ4 genotype had substantial aberrations in blood lipid levels. In Kaplan-Meier curves, statistically significant differences were revealed in the prognosis of survival within the subgroup of females who had a myocardial infarction (p = 0.0006): the prognosis was worse for carriers of the ɛ2/ɛ2 genotype and for ɛ4/ɛ4 carriers. Survival analysis regarding deaths from all causes showed (p = 0.0238) that female carriers of the ɛ2/ɛ4 genotype had a worse prognosis than did carriers of other genotypes. Thus, in the population of Western Siberia (Russia), we confirmed statistically significant associations between rs7412 & rs429358 genotypes and lipid profile parameters.

The Relationship between Epigenetic Age and Myocardial Infarction/Acute Coronary Syndrome in a Population-Based Nested Case-Control Study.

We investigated the relationship between 'epigenetic age' (EA) derived from DNA methylation (DNAm) and myocardial infarction (MI)/acute coronary syndrome (ACS). A random population sample was examined in 2003/2005 (n = 9360, 45-69, the HAPIEE project) and followed up for 15 years. From this cohort, incident MI/ACS (cases, n = 129) and age- and sex-stratified controls (n = 177) were selected for a nested case-control study. Baseline EA (Horvath's, Hannum's, PhenoAge, Skin and Blood) and the differences between EA and chronological age (CA) were calculated (ΔAHr, ΔAHn, ΔAPh, ΔASB). EAs by Horvath's, Hannum's and Skin and Blood were close to CA (median absolute difference, MAD, of 1.08, -1.91 and -2.03 years); PhenoAge had MAD of -9.29 years vs. CA. The adjusted odds ratios (ORs) of MI/ACS per 1-year increments of ΔAHr, ΔAHn, ΔASB and ΔAPh were 1.01 (95% CI 0.95-1.07), 1.01 (95% CI 0.95-1.08), 1.02 (95% CI 0.97-1.06) and 1.01 (0.93-1.09), respectively. When classified into tertiles, only the highest tertile of ΔAPh showed a suggestion of increased risk of MI/ACS with OR 2.09 (1.11-3.94) independent of age and 1.84 (0.99-3.52) in the age- and sex-adjusted model. Metabolic modulation may be the likely mechanism of this association. In conclusion, this case-control study nested in a prospective population-based cohort did not find strong associations between accelerated epigenetic age markers and risk of MI/ACS. Larger cohort studies are needed to re-examine this important research question.

Association of RS708272 (CETP Gene Variant) with Lipid Profile Parameters and the Risk of Myocardial Infarction in the White Population of Western Siberia.

: The TaqI B (rs708272) single-nucleotide variant, i.e., the +279 G/A substitution in intron 1 of the CETP gene, is actively investigated as a risk factor of lipid metabolism disorders. The aim of this study was to analyze the association of rs708272 with lipid parameters and the risk of myocardial infarction in the population of Western Siberia (Russia). The study population was selected from a sample surveyed within the framework of the Health, Alcohol and Psychosocial Factors In Eastern Europe (HAPIEE) study (9360 participants, >90% white, aged 45-69 years, males: 50%). In total, 3132 randomly selected patients were included. Plasma lipid levels were determined by standard enzymatic assays. Rs708272 was analyzed by RT-PCR via TaqMan single-nucleotide polymorphism (SNP) Genotyping Assays (Thermo Fisher Scientific, USA). The frequencies of rs708272 genotypes AA (homozygote), AG (heterozygote), and GG were 0.21, 0.49, and 0.30, respectively, in this population. Allele A frequency was 0.46. We found an association of allele G with low levels of high-density lipoprotein cholesterol and a high index of atherogenicity in this population (p < 0.001 and p < 0.001, respectively). Allele G was significantly associated with the risk of myocardial infarction among the male participants (odds ratio 1.96, 95% confidence interval 1.208-3.178, p = 0.008) and in the study population (odds ratio 1.465, 95% confidence interval 1.028-2.087, p = 0.036). Thus, rs708272 is associated with myocardial infarction in the white population of Western Siberia (Russia).

Analysis of Polymorphism rs1333049 (Located at 9P21.3) in the White Population of Western Siberia and Associations with Clinical and Biochemical Markers.

The 9p21.3 chromosomal region is a marker of the risk of cardiovascular diseases. The aim of this study was to analyze single-nucleotide polymorphism rs1333049 (chr9:22125504) in the population of Western Siberia (Russia) and possible associations with clinical and biochemical parameters. The population included in the analyses was selected from a sample surveyed within the framework of the Health, Alcohol and Psychosocial Factors In Eastern Europe (HAPIEE) study (9360 participants, >90% white, aged 45-69, males: 50%). In total, 2729 randomly selected patients were included. Plasma lipid levels were determined by standard enzymatic assays. Rs1333049 was analyzed by RT-PCR (BioLabMix, Russia). Frequencies of rs1333049 genotypes C/C (homozygote), C/G (heterozygote), and G/G were 0.22, 0.51, and 0.27 in this population. The Allele G frequency was 0.53. We found an association of allele G with total cholesterol and low-density lipoprotein cholesterol levels among male participants (p = 0.004 and p = 0.002, respectively). Allele C was significantly associated with the risk of myocardial infarction among the male participants (odds ratio 1.96, 95% confidence interval 1.14-3.38, p = 0.017) and the study population (odds ratio 1.83, 95% confidence interval 1.23-2.72, p = 0.004). Thus, rs1333049 is associated with myocardial infarction in the white population of Western Siberia (Russia).

Leukocyte telomere length and risk of coronary heart disease and stroke mortality: prospective evidence from a Russian cohort.

Previous studies suggest that reduced leukocyte telomere length (LTL) is related to higher risk of mortality and several chronic conditions, including coronary heart disease (CHD) and stroke. However, the consistency of this association differs across populations. We investigated the relationship of LTL with CHD, stroke and all-cause mortality together with non-fatal CHD and stroke events in a Russian cohort with a mean age of 58 years at baseline. Data from 1,144 individuals in the Russian subset of the Health Alcohol and Psychosocial Factors in Eastern Europe (HAPIEE) cohort study were used. The associations between LTL at baseline and fatal/non-fatal outcomes during 12 years of follow-up were assessed using multivariable Cox regression models, which yielded adjusted hazard ratios (HR). Compared to individuals in the shortest tertile, those in the longest tertile of LTL had a 42% lower risk of death from all-causes (HR 0.58; 95% CI: 0.39-0.88) and 58% lower risk of death from CHD (HR 0.42; 95%CI: 0.19-0.97). Similar patterns of association were identified for non-fatal and combined fatal/non-fatal CHD and stroke events but the associations were weaker. Consistent with results of previous studies in Western populations, this cohort of elderly Russian adults found an inverse association between LTL and CHD and all-cause mortality. These findings reinforce the hypothesis that LTL may play (or be a marker of) an aetiological role in human health across diverse populations.

The influence of social support on risk of acute cardiovascular diseases in female population aged 25-64 in Russia.

OBJECTIVE: To study the prevalence of social support (SS) and its influence on the relative risk (RR) of myocardial infarction (MI) and stroke in the female population aged 25-64 in Russia. MATERIALS AND METHODS: Under the third screening of the WHO "MONICA-psychosocial" programme, a random representative sample of women aged 25-64 (n=870) were surveyed in Novosibirsk. SS was measured according to the methods of the Berkman-Sym test [indices of close contacts (ICC) and index of social network (SNI)]. From 1995 to 2010, women were followed for 16 years to observe the incidence of MI and stroke. RESULTS: The prevalence of low levels of ICC and SNI in women aged 25-64 was 57.1 and 77.7%, respectively. Low levels of ICC and SNI were associated with poor self-rated health and awareness about their health, adverse behavioral habits, high job strain and family stress. Rates of MI and stroke development were higher in married women with low ICC and SNI who were being in class "hard manual work". Over a 16-year study period, the RR of MI in women with low ICC compared to those with high ICC was 4.9 times higher, and the risk of stroke was 4.1 times higher. Low level of SNI increased MI risk in 2.9 times, risk of stroke in 2.7 times. CONCLUSION: Majority of women aged 25-64 years in Russia have low social support which is associated with poor self-rated health, low awareness about the health that increases the risk of MI and stroke in 2.7-4.9 times in groups of "married" and "hard physical work".

The influence of depression on risk development of acute cardiovascular diseases in the female population aged 25-64 in Russia.

BACKGROUND: Recent studies showed that depression was an independent predictor of mortality from cardio-vascular disease in healthy women. OBJECTIVE: To explore the effect of depression (D) on relative risk (RR) of myocardial infarction (MI) and stroke for 16 years (1995-2010) in the female population aged 25-64 years from Novosibirsk, Russia. MATERIALS AND METHODS: Under the third screening of the WHO "MONICA-psychosocial" (MOPSY) programme, a cohort of women aged 25-64 years (N=560) was surveyed. Women were followed for 16 years for the incidence of MI and stroke (1995-2010). D was measured at the baseline examination by means of test "MOPSY". Participants having stroke, MI, arterial hypertension, coronary artery diseases and diabetes in their medical history at the baseline were excluded from this analysis. RESULTS: The prevalence of D in women aged 25-64 years was 55.2%. With the growth of D levels, positive self-rated health reduced and almost 100% of those women have complaints about their health, but considered the care of their health insufficient. Women with major D significantly extended negative behavioral habits: smoking and unsuccessful attempts to give up, low physical activity, and less likely to follow a diet (healthy food). Major D associated with high job strain and family stress. Relative risk (RR) of MI development in women with D during 16 years of study was higher in 2.53 cases (p<0.05) and risk of stroke was higher in 4.63 cases (p<0.05). CONCLUSIONS: The prevalence of D in women aged 25-64 years was >50%. Women with D had a 2.53-fold risk of MI and 4.63-fold risk of stroke during the 16 years of follow-up.

Education, marital status, and total and cardiovascular mortality in Novosibirsk, Russia: a prospective cohort study.

PURPOSE: Mortality from cardiovascular diseases in Russia is among the highest in the world but little is known about its distribution by socio-demographic factors. We investigated this question in a prospective cohort study based on the Novosibirsk MONICA Project. METHOD: The cohort consisted of 6485 men and 4919 women aged 25 to 64 years at baseline, examined in 4 surveys in 1984, 1985/86, 1988/89, and 1994/95, and followed up for an average 10.3 (range 3.1-15.2) years. Participants reported their education and marital status in a questionnaire; the information on risk factors was collected in a short medical examination. RESULTS: A total of 836 male and 226 female deaths occurred during the follow up. High education was associated with reduced mortality from all causes, cardiovascular disease, and coronary heart disease in both genders. Age-adjusted relative risk of death from cardiovascular diseases for university vs. primary education was 0.6 (0.4-0.8) in men and 0.4 (0.2-0.8) in women. Adjustment for coronary risk factors and marital status substantially reduced the relative risk in men but not in women. There was no consistent relation between education and stroke. Unmarried men had higher mortality from all causes, cardiovascular and coronary heart disease than married subjects; the increased risk of divorced men was not explained by coronary risk factors or low education. Unmarried women had higher all-cause mortality than married women but associations between marital status and cardiovascular diseases were inconsistent. CONCLUSION: The educational differences in total and cardiovascular mortality in Russia are of similar direction and magnitude as in western populations. The educational differences in cardiovascular mortality in women and the increased mortality of divorced men were not explained by classical risk factors.

Relation between heavy and binge drinking and all-cause and cardiovascular mortality in Novosibirsk, Russia: a prospective cohort study.

BACKGROUND: Moderate alcohol consumption is associated with reduced cardiovascular mortality, but binge drinking is thought to be detrimental. We examined effects of heavy and binge drinking in a population with high rates of binge drinking. METHODS: We did a prospective cohort study in Novosibirsk, Russia, in 6502 men aged 25-64 years at baseline who were examined in WHO MONICA (monitoring trends and determinants in cardiovascular disease surveys) in 1985/86, 1988/89, and 1994/95, and in a pilot study in 1984. We assessed alcohol intake and drinking pattern by questionnaire; binge drinking was defined as consumption of 160 g or greater of pure alcohol on a typical occasion. Participants were followed-up for a median of 9.5 years (range 3.1-15.2). FINDINGS: There were 836 deaths in the cohort, 395 of which resulted from cardiovascular diseases. Prevalence of binge drinking at baseline was 16% (n=1005). Adjusted relative risks for binge drinking at least once a month (compared with consumption of <80 g pure alcohol) were 1.05 (95% CI 0.80-1.36) for deaths from all causes, 0.99 (0.66-1.50) for deaths from cardiovascular disease, 1.27 (0.81-1.99) for deaths from coronary heart disease, and 2.08 (1.08-3.99) for death from external causes. Risk of total and cardiovascular mortality was raised in a small group of frequent heavy drinkers (5% [264] of all drinkers); for this group, adjusted relative risks were 1.61 (1.04-2.50) for total mortality and 2.05 (1.09-3.86) for deaths from cardiovascular disease. INTERPRETATION: The risk of death from cardiovascular disease seems to be increased in frequent heavy drinkers, but is not necessarily associated with episodic binge drinking.