ABCA3 and LZTFL1 Polymorphisms and Risk of COVID-19 in the Czech Population.

SARS-CoV-2 infection, which causes the respiratory disease COVID-19, has spread rapidly from Wuhan, China, since 2019, causing nearly 7 million deaths worldwide in three years. In addition to clinical risk factors such as diabetes, hypertension, and obesity, genetic variability is an important predictor of disease severity and susceptibility. We analyzed common polymorphisms within the LZTFL1 (rs11385942) and ABCA3 (rs13332514) genes in 519 SARS-CoV-2-positive subjects (164 asymptomatic, 246 symptomatic, and 109 hospitalized COVID-19 survivors) and a population-based control group (N?=?2,592; COVID-19 status unknown). Rare ABCA3 AA homozygotes (but not A allele carriers) may be at a significantly increased risk of SARS-CoV-2 infection [P?=?0.003; OR (95 % CI); 3.66 (1.47-9.15)]. We also observed a borderline significant difference in the genotype distribution of the LZTFL1 rs11385942 polymorphism (P?=?0.04) between the population sample and SARS-CoV-2-positive subjects. In agreement with previous studies, a nonsignificantly higher frequency of minor allele carriers was detected among hospitalized COVID-19 subjects. We conclude that a common polymorphism in the ABCA3 gene may be a significant predictor of susceptibility to SARS-CoV-2 infection.

A haemochromatosis-causing HFE mutation is associated with SARS-CoV-2 susceptibility in the Czech population.

BACKGROUND: Coronavirus disease (COVID-19), which is caused by the SARS-CoV-2 virus, has become a global pandemic. While susceptibility to COVID-19 is subject to several external factors, including hypertension, BMI, and the presence of diabetes, it is also genetically determined to a significant extent. Infectious agents require iron (Fe) for proper functioning. Carriers of mutations resulting in increased iron concentrations are understood to be at increased risk of COVID-19. METHODS: We examined HFE genotypes associated with hereditary haemochromatosis (rs1800562 and rs1799945 SNPs) in 617 COVID-19 patients (166 asymptomatic, 246 symptomatic and 205 hospitalised survivors) and 2 559 population-based controls. RESULTS: We found a higher frequency of the minor allele (Tyr282) of the rs1800562 polymorphism (P < 0.002) in patients compared to controls (8.5 % vs 5.5 %). Non-carriers of the minor allele were protected against SARS-Cov-2 infection (OR, 95 %CI; 0.59, 0.42-0.82). The frequency of minor allele carriers was almost identical across asymptomatic, symptomatic, and hospitalised survivors. The rs1799945 variant did not affect disease severity and its occurrence was almost identical in patients and controls (P between 0.58 and 0.84). CONCLUSIONS: In conclusion, our results indicate that presence of the rs1800562 minor allele, which is associated with hereditary haemochromatosis (thus increased levels of plasma Fe), increases susceptibility to SARS-CoV-2.

[Cognitive functions and modifiable risk factors for chronic non-communicable diseases in ageing in a Russian population sample.]

We aimed to investigate the relationship between the indicators of cognitive functions (CF) and modifiable risk factors for chronic non-communicable diseases (NCD) in a cross-sectional analysis in the urban Russian population sample aged 55-84 years. The study investigated a random sample of 3 153 people (men and women 55-84 years old) from a general population cohort of Novosibirsk residents; a sample was examined within the international project HAPIEE. The study protocol included standardized neuropsychological tests (quantitative assessment of memory, semantic verbal fluency, attention and processing speed) and standardized assessment of risk factors, history and treatment of cardiovascular disease and NCD. In cross-sectional analysis we observed a positive relationship of CF indices with level of education and an inverse relationship with metabolic risk factors and smoking in both sexes. The level of total cholesterol and moderate alcohol consumption had positive relationship with CF indices in women. These associations were independent from age and other factors.

Genetics of T2DM and Its Chronic Complications: Are We Any Closer to the Individual Prediction of Genetic Risk?

Type 2 diabetes mellitus (T2DM) is a complex disease that has risen in global prevalence over recent decades, resulting in concomitant and enormous socio-economic impacts. In addition to the well-documented risk factors of obesity, poor dietary habits and sedentary lifestyles, genetic background plays a key role in the aetiopathogenesis of diabetes and the development of associated micro- and macrovascular complications. Recent advances in genomic research, notably next-generation sequencing and genome- wide association studies, have greatly improved the efficiency with which genetic backgrounds to complex diseases are analysed. To date, several hundred single-nucleotide polymorphisms have been associated with T2DM or its complications. Given the polygenic background to T2DM (and numerous other complex diseases), the degree of genetic predisposition can be treated as a "continuous trait" quantified by a genetic risk score. Focusing mainly on the Central European population, this review summarizes recent state-of-the-art methods that have enabled us to better determine the genetic architecture of T2DM and the utility of genetic risk scores in disease prediction.

Effects of selected inherited factors on susceptibility to SARS-CoV-2 infection and COVID-19 progression.

Genetic predispositions may influence geographical and interethnic differences in COVID-19 prevalence and mortality in affected populations. Of the many genes implicated in COVID-19 progression, a substantial number have no direct functional link on virus transfer/viability or on the host immune system. To address this knowledge deficit, a large number of in silico studies have recently been published. However, the results of these studies often contradict the findings of studies involving real patients. For example, the ACE2 has been shown to play an important role in regulating coronavirus entry into cells, but none of its variations have been directly associated with COVID-19 susceptibility or severity. Consistently was reported that increased risk of COVID-19 is associated with blood group A and with the APOE4 allele. Among other genes with potential impacts are the genes for CCR5, IL-10, CD14, TMPRSS2 and angiotensin-converting enzyme. Variants within the protein-coding genes OAS1 and LZTFL1 (transferred to the human genome from Neanderthals) are understood to be among the strongest predictors of disease severity. The intensive research efforts have helped to identify the genes and polymorphisms that contribute to SARS-CoV-2 infection and COVID-19 severity.

The role of connexin 37 polymorphism in spontaneous abortion.

Among unique cardiovascular risk factors in women are complications during pregnancy, including miscarriage. Important risk factor is also genetic background. One of powerful candidate genes for cardiovascular disease of atherosclerotic origin (aCVD) is gene for connexin 37 (Cx37) with strong gene-environment interaction including smoking status, that is also strong risk factor for complications in pregnancy including spontaneous abortion (SA). We analyzed association between SA and Cx37 gene polymorphism (1019C>T; Pro319Ser) in 547 fetuses and its potential interaction with smoking status of mothers. Using genetic analyses from women from general population as controls, ORs for T allele, found in our previous studies to be protective against aCVD, were calculated. T allele carriers (fetuses), had OR 0.91 (95 % CI 0.72-1.14) and no interaction with smoking was observed. In conclusion, no significant association between Cx37 polymorphism and SA was observed and no modifying effect of smoking status on this association was detected.

CCR5Delta32 deletion as a protective factor in Czech first-wave COVID-19 subjects.

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease (COVID-19), has spread widely around the globe. Significant inter-individual differences have been observed during the course of the infection, which suggests that genetic susceptibility may be a contributing factor. CC chemokine receptor 5 (CCR5), which acts as a co-receptor for the entry of HIV-1 into cells, is promising candidate whose can have an influence on SARS-CoV-2 infection. A genetic mutation known as CCR5Delta32, consisting of a 32-nucleotide deletion, encodes a truncated protein that protects homozygous carriers of the deletion from HIV-1 infection. Similarly, inhibition of CCR5 seems to be protective against COVID-19. In our study, we successfully genotyped 416 first-wave SARS-CoV-2-positive infection survivors (164 asymptomatic and 252 symptomatic) for CCR5?32, comparing them with a population based sample of 2,404 subjects. We found the highest number (P=0.03) of CCR5Delta32 carriers in SARS-CoV-2-positive/COVID-19-asympto-matic subjects (23.8 %) and the lowest number in SARS-CoV-2-positive/COVID-19-symptomatic patients (16.7 %), with frequency in the control population in the middle (21.0 %). We conclude that the CCR5?32 I/D polymorphism may have the potential to predict the severity of SARS-CoV-2 infection.

[The frequency and profile of drug treatment in subjects with dyslipidemias and cardimetabolic diseases in an urban russian population older then 55 years].

Aim      To analyze frequency and profile of the lipid-lowering therapy (LLT) in patients with dyslipidemia (DLP) and cardiometabolic diseases (CMD) in a population sample aged 55-84 years at the current time (2015-2017).Material and methods  Despite guidelines on DLP treatment and the availability of effective and safe lipid-lowering drugs, control of DPL in primary and secondary prevention of cardiovascular diseases (CVD) is insufficient. Knowledge of the level of pharmaceutical correction of DLP in the Russian population is limited; it requires an LLT assessment in various regions and in a wide age range, and a regular monitoring taking into account changing approaches to the correction of DLP. A random population of men and women aged 55-84 years (n=3 896) was evaluated in Novosibirsk in 2015-2017 (project HAPIEE). A joint DLP category was established as low-density lipoprotein cholesterol (LDL-C) ≥3.0 mmol/l, or total cholesterol (TC) ≥5.0 mmol/l, or triglycerides (TG) ≥1.7 mmol/l, or LLT. The combined group of DLP and CMD included ischemic heart disease (IHD), type 2 diabetes mellitus (DM2), and DLP. Regular LLD treatment for the recent 12 months, excluding the dosage of medicines, was assessed using the Anatomic Therapeutic Chemical (ATC) classification. The conditional control of serum lipids was taken as the achievement of LDL-C <3.0 mmol/l, TC <5.0 mmol/l, and TG <1.7 mmol/l.Results In the study sample, the total prevalence of DLP and CMD was 88 % (82.8 % for men and 91.3 % for women, p<0.001). 48.3% of patients in the IHD group, 35.0% in the DM2 group, 29.4% in the DLP group, and 32.8% in the CMD group took LLT. Control of serum lipids was achieved in 18.3% (37.9 % of patients on LLT) of patients with IHD; 9 % (25.6 % of patients on LLT) of patients with DM2; 7.3 % (24.8 % of patients on LLT) of patients with DLP; and 9.0 % (27.6 % of patients on LLTсреди) in the DLP and CMD group. Women with DM2 and DLP more frequently achieved lipid control than men (p<0.001). 98.7 % of study participants took statins as LLT.Conclusion      In the sample of urban population aged 55-84 years in 2015-2017, 90 % of patients had DLP or CMD, and at least ¾ of them required blood lipid control. The lipid control was achieved in every fifth IHD patient and in approximately 40% of those who took LLT. For DM2 or DLP patients, the lipid control was achieved in every tenth patient and in approximately 25% of those receiving LLT. Frequency of lipid control in IHD patients was comparable for men and women; in DM2 and DLP, men less frequently achieved the lipid control than women. About 70% of patients in the combined DLP and CMD group and more than 50% of IHD patients did not take LLT, which considerably contributed to the insufficient lipid control in primary and secondary prevention of atherosclerotic CVDs in this population.

Global DNA methylation in rats´ liver is not affected by hypercholesterolemic diet.

Increased plasma cholesterol levels are listed between the major atherosclerosis risk factors. The final plasma cholesterol levels result from the interplay between the genetic and environmental (diet, physical activity) factors. Little is known, how dietary factor influence epigenetics. We have analyzed, if an over-generation feeding of rat with cholesterol influences total liver-DNA methylation, and if total liver-DNA methylation differ between the different rat strains (Prague hereditary hypercholesterolemic rats, Prague hereditary hypertriglyceridemic rats and Wistar Kyoto rats). The animals were feed with high fat (additional 5 % over normal capacity) high cholesterol (2 %) diet for 14 days. DNA methylation in the liver tissue in different generations was analyzed using the liquid chromatography coupled with tandem mass spectrometry. We have not observed any significant changes in total liver-DNA methylation over the 9 generations of animals feed by fat/cholesterol enriched diet. Additionally, there were no differences in DNA methylation between different rat strains. In animal model, the dietary changes (hypercholesterolemic diet) not significantly influence the total DNA methylation status within the liver.

Genetic Markers at ANRIL, FTO and 2q36.3 Locus in Czech Patients Undergoing Coronary Artery Bypass Graft Surgery.

Coronary artery bypass graft (CABG) surgery is one of the most commonly performed operations worldwide. We compared genotype frequencies of three major cardiovascular disease (CVD)-associated genetic markers (ANRIL, FTO and 2q36.3 locus) between 753 patients who underwent CABG at the Institute for Clinical and Experimental Medicine (Prague, Czech Republic) and 2,559 controls from the Czech post-MONICA study. Subjects with at least one major A allele in the rs10757274 polymorphism (ANRIL) were more prevalent in patients after CABG than in the controls (81.7 % vs 72.7 %; OR [95 % CI] 1.67 [1.35-2.05]; P < 0.0001). In contrast, variants within the FTO gene (OR 0.87; 95 % CI, 0.70-1. 09 in a TT vs. GG comparison, P = 0.24) and 2q36.3 locus (OR 1.16; 95% CI, 0.98-1.37 in a +A vs. CC comparison, P = 0.08) were not significantly associated with CVD in our study. Variants were not associated with anthropometric, biochemical, or clinical characteristics within the patient group. Our study suggests that patients with CABG are more commonly carriers of some but not all CVD-associated alleles.

Strong Association between APOA5 Gene Polymorphisms and Hypertriglyceridaemic Episodes.

Plasma triglyceride (TG) levels represent a significant risk factor of cardiovascular and total mortality. Concentrations of TG in the plasma depend, to a large extent, on the genetic background, and the apolipoprotein A5 (APOA5) gene seems to be one of the most powerful players in the plasma TG metabolism regulation. In total, we analysed three tagging APOA5 (rs964184 rs662799, rs3135506) SNPs in 209 patients with plasma TG levels over 10 mmol/l (HTG) on at least one occasion and in 379 treatment-naïve controls (NTG) with plasma TG values within the normal range. Minor alleles of all three analysed APOA5 polymorphisms significantly (all P < 0.0001) increased the risk of hypertriglyceridaemia. The most significant association (P < 0.0000001) was observed for the rs964184 polymorphism, where the minor GG homozygotes had the odds ratio (OR, 95% CI) for hypertriglyceridaemia development 21.30 (8.09-56.07, P < 0.000001) in comparison with the major CC allele homozygotes. Carriers of at least one minor allele at rs3135506 had OR (95% CI) 4.19 (2.75-6.40); (P < 0.000005) for HTG development and similarly, carriers of a minor allele at rs662799 had OR (95% CI) 3.07 (2.00-4.72) (P < 0.0001). The cumulative presence of risk alleles (unweighted gene score) significantly differed between patients with episodes of high TG and controls at P < 0.0000001. There were 73 % of subjects without any of the risk alleles among the controls and 46 % in the patients. In contrast, the controls just included 3 % of subjects with score 3 and more in comparison with 18 % in HTG patients. We conclude that common APOA5 variants are very important genetic determinants of episodic hypertriglyceridaemia in the Czech population with a high potential to be applied in personalized medicine.

Aldehyde dehydrogenase 2 polymorphism affects the outcome of methanol poisoning in exposed humans.

As the susceptibility of humans to xenobiotics often depends on genetic factors, we assumed that ADH1B and ALDH2 genetic variants may affect susceptibility to the acute methanol exposure. To evaluate the role of genetic variants of enzymes involved in methanol catabolism in humans, we analysed ADH1B (rs1229984) and ALDH2 (rs441) polymorphisms in 50 adults who survived acute methanol poisoning, 246 individuals with alcoholic liver cirrhosis, and in 545 healthy controls. GG homozygotes of ADH1B were more common among methanol-poisoned patients (98%) and among patients with alcoholic liver cirrhosis (98%) than among healthy controls (90%) (P = 0.08 and < 0.001, respectively). Minor C allele carriers of the ALDH2 were significantly more common among methanol-poisoned persons (46%) than among patients with alcoholic liver cirrhosis or healthy controls (31% in both groups, P < 0.05 and 0.025, respectively); the odds ratios were 1.89 (95% CI 1.02-3.52) and 1.94 (1.08-3.48), respectively. As there was a substantial amount of subjects with alcohol abuse between both groups of patients, ADH1B is unlikely to affect the susceptibility to methanol poisoning. By contrast, the genetic variant of the ALDH2 enzyme seems to specifically affect the susceptibility to methanol in acutely exposed humans and potentially plays a role in the outcome of methanol poisoning.

Regulatory RNAs and cardiovascular disease - with a special focus on circulating microRNAs.

MicroRNAs (miRNAs) are a class of short non-coding regulatory RNA molecules which play an important role in intracellular communication and cell signaling and which influence cellular processes such as proliferation, differentiation, and cellular death. Over the past two decades, the crucial role of microRNAs in controlling tissue homeostasis and disease in cardiovascular systems has become widely recognized. By controlling the expression levels of their targets, several miRNAs have been shown to modulate the function of endothelial cells (miR-221/222 and -126), vascular smooth muscle cells (miR-143/145) and macrophages (miR-33, -758, and -26), thereby regulating the development and progression of atherosclerosis. The stability of miRNAs within the blood suggests that circulating miRNAs may function as important biomarkers of disease development and progression. Numerous circulating miRNAs have been found to be dysregulated in a wide variety of different disease states, including diabetes, cancer, and cardiovascular disease.

Polygenic hypercholesterolemia: examples of GWAS results and their replication in the Czech-Slavonic population.

Since 2007, the year of their first widespread use, genome-wide association studies (GWAS) have become the "gold standard" for the detection of causal genes and polymorphisms in all fields of human medicine. Cardiovascular disease (CVD), one of the major causes of morbidity and mortality, is no exception. The first GWAS focused on hypercholesterolemia and dyslipidemia as the major CVD determinants. GWAS confirm the importance of most of the previously identified genes (e.g. APOE, APOB, LDL-R) and recognize the importance of new genetic determinants (e.g. within the CILP2 or SORT1 gene clusters). Nevertheless, the results of GWAS still require confirmation by independent studies, as interethnic and interpopulation variability of SNP effects have been reported. We analyzed an association between eight variants within seven through GWAs detected loci and plasma lipid values in the Czech post-MONICA population sample (N=2,559). We confirmed an association (all P<0.01) between plasma LDL-cholesterol values and variants within the CILP2 (rs16996148), SORT1 (rs646776), APOB (rs693), APOE (rs4420638) and LDL-R (rs6511720) genes in both males (N=1,194) and females (N=1,368). In contrast, variants within the APOB (rs515135), PCSK9 (rs11206510) and HMGCoAR (rs12654264) genes did not significantly affect plasma lipid values in Czech males or females. Unweighted gene score values were linearly associated with LDL-cholesterol values both in males (P<0.0005) and females (P<0.00005). We confirmed the effects of some, but not all analyzed SNPs on LDL-cholesterol levels, reinforcing the necessity for replication studies of GWA-detected gene variants.

Traditional risk factors of acute coronary syndrome in four different male populations - total cholesterol value does not seem to be relevant risk factor.

Cardiovascular diseases are the most common cause of mortality and morbidity in most populations. As the traditional modifiable risk factors (smoking, hypertension, dyslipidemia, diabetes mellitus, and obesity) were defined decades ago, we decided to analyze recent data in patients who survived acute coronary syndrome (ACS). The Czech part of the study included data from 999 males, and compared them with the post-MONICA study (1,259 males, representing general population). The Lithuanian study included 479 male patients and 456 age-matched controls. The Kazakhstan part included 232 patients and 413 controls. In two countries, the most robust ACS risk factor was smoking (OR 3.85 in the Czech study and 5.76 in the Lithuanian study), followed by diabetes (OR 2.26 and 2.07) and hypertension (moderate risk elevation with OR 1.43 and 1.49). These factors did not influence the ACS risk in Kazakhstan. BMI had no significant effect on ACS and plasma cholesterol was surprisingly significantly lower (P<0.001) in patients than in controls in all countries (4.80+/-1.11 vs. 5.76+/-1.06 mmol/l in Czechs; 5.32+/-1.32 vs. 5.71+/-1.08 mmol/l in Lithuanians; 4.88+/-1.05 vs. 5.38+/-1.13 mmol/l in Kazakhs/Russians). Results from our study indicate substantial heterogeneity regarding major CVD risk factors in different populations with the exception of plasma total cholesterol which was inversely associated with ACS risk in all involved groups. These data reflect ethnical and geographical differences as well as changing pattern of cardiovascular risk profiles.

SNPs within CHRNA5-A3-B4 and CYP2A6/B6 are associated with smoking dependence but not with tobacco dependence treatment outcomes in the Czech population.

PURPOSE: Tobacco/nicotine dependence has a significant heritable component. Genome-wide association studies have associated the single nucleotide polymorphisms (SNPs) rs578776, rs16969968, rs6474412, rs3733829 and rs4105144 with nicotine dependence in Western European populations. We examined whether these SNPs influence nicotine dependence and successful treatment of tobacco dependence in the Czech middle-European population. MATERIALS AND METHODS: Variants were analysed by PCR-RFLP or by TaqMan assay in 807 adult heavy tobacco-dependent smokers - patients of the Centre for Treatment of Tobacco Dependence (Prague) as well as 1,362 self-reported non-smokers. RESULTS AND DISCUSSION: Except for rs3733829, association with tobacco dependence was confirmed for all other genetic variants. In agreement with previous studies, the strongest determinant of tobacco dependence was rs16969968 with OR (95%CI) 1.32 (1.08-1.62) for A allele carriers vs. GG comparison (P=0.003). In contrast, none of the analysed variants reached significance with respect to a 1-year course of successful tobacco dependence treatment (all P over 0.18) in a subset of 525 patients. CONCLUSION: We confirmed the association between variants within genes that code nicotinic-acetylcholine receptors (-A3, -A5 and -B3), CYP2A6/B6 and tobacco dependence development in the Czech population. The success of the tobacco dependence treatment was not influenced by the analysed SNPs.

Can Leukocyte Telomere Length Predict Survival Time in Heart Transplant Recipients over a Minimal Follow-Up of 20 years?

In humans, leukocyte telomere length (LTL) reduces with age and is reported to be inversely associated with ageing-related diseases. We measured LTL in leukocyte DNA using a quantitative PCR-based method from 127 blood samples of heart recipients (107 males, 20 females, age 44.1 ± 10.5), followed for up to 30 years. Patients with coronary artery disease survived for a shorter time and also had shorter LTL (both P < 0.05 after adjustment for age and sex) than subjects with dilated cardiomyopathy. Patients with non-cardiac causes of death had shorter LTL than patients with cardiac causes (P < 0.05 after adjustment for age). An inverse correlation between LTL and age (P < 0.03) was observed in patients with non-cardiac causes of death only. Most importantly, LTL was not associated with general survival time in patients after heart transplantation. However, shorter LTL was a marker of non-cardiac causes of death. Different LTLs and survival times were determined in association with aetiology of heart failure (HF).

Gene variants at FTO, 9p21, and 2q36.3 are age-independently associated with myocardial infarction in Czech men.

AIM: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in developed countries. This study aimed to confirm the effect of common putative CVD-associated gene variants (FTO rs17817449, KIF6 rs20455, 9p21 rs10757274 and 2q36.3 rs2943634) on CVD manifestation, and determine whether this effect differs between younger (< 50 years) and older CVD patients. METHODS: 1191 controls and 1889 MI patients were analyzed. All participants were Caucasian Czech males aged <65 years (532 were <50 years) who were examined at cardiology clinics in Prague, Czech Republic. Variants of FTO, 9p21, 2q36.3, and KIF-6 were genotyped using PCR-RFLP or TaqMan assay. RESULTS: Variants of FTO (OR 1.48; 95% CI, 1.19-1.84 in a TT vs. GG comparison, p=0.0005); 9p21 (OR 1.74; 95% CI, 1.41-2.14 in an AA vs. GG comparison, p=0.0001); and 2q36.3 (OR 1.34; 95%CI, 1.09-1.65 in an AA vs. +C comparison, p=0.006) were significantly associated with MI in the male Czech population. In contrast, genotype frequencies of KIF-6 (rs20455) were the same in patients and controls (P=1.00). Nearly identical results were observed when a subset of young MI patients (N=532, aged <50 years) was analyzed. CONCLUSION: We confirmed the importance of determining FTO, 9p21, and 2q36.3 variants as part of the genetic determination of MI risk in the Czech male population.

Genetic predisposition of human plasma triglyceride concentrations.

The issue of plasma triglyceride levels relative to the risk of development of cardiovascular disease, as well as overall mortality, has been actively discussed for many years. Like other cardiovascular disease risk factors, final plasma TG values have environmental influences (primarily dietary habits, physical activity, and smoking), and a genetic predisposition. Rare mutations (mainly in the lipoprotein lipase and apolipoprotein C2) along with common polymorphisms (within apolipoprotein A5, glucokinase regulatory protein, apolipoprotein B, apolipo-protein E, cAMP responsive element binding protein 3-like 3, glycosylphosphatidylinositol-anchored HDL-binding protein 1) play an important role in determining plasma TG levels.

Association between fasting plasma triglycerides, all-cause and cardiovascular mortality in Czech population. Results from the HAPIEE study.

Dyslipidemia is the risk factor of cardiovascular disease, but the relationship between the plasma triglyceride (TG) levels and total/cardiovascular mortality has not yet been analyzed in Slavs. The aim of our study was to analyze the association between the fasting TG levels and all-cause/cardiovascular mortality. We have examined 3,143 males and 3,650 females, aged 58.3+/-7.1 years. 729 deaths (274 cardiovascular deaths) have been registered during up to 11.8 years of follow-up. Age-sex adjusted all-cause mortality was higher in individuals with TG values 3.01-4.00 mmol/l (HR 1.37, 95 % CI 1.02-1.83, P=0.035) and over 4.00 mmol/l (HR 1.66, 95 % CI 1.21-2.27, P=0.002) when compared with a reference group (TG 1.41-1.80 mmol/l). Elevated risk remains significant when adjusted for education, marital status and unemployment. When further adjusted for smoking, BMI and dyslipidemia interventions, HR for those in above 4.00 mmol/l group decreased (1.42, P=0.04). The results have been similar when cardiovascular mortality has been examined, however, results reached statistical significance only for the TG over 4.0 mmol/l (P=0.028). Our results confirmed that enhanced plasma levels of plasma triglycerides are dose dependently associated with increased risk of all-cause mortality, however, it seems that individuals with TG values 1.8-3.0 mmol/l are not in higher risk of death.