This study investigated 12-year blood lipid trajectories and whether these trajectories are modified by smoking and lipid lowering treatment in older Russians. To do so, we analysed data on 9,218 Russian West-Siberian Caucasians aged 45-69 years at baseline participating in the international HAPIEE cohort study. Mixed-effect multilevel models were used to estimate individual level lipid trajectories across the baseline and two follow-up examinations (16,445 separate measurements over 12 years). In all age groups, we observed a reduction in serum total cholesterol (TC), LDL-C and non-HDL-C over time even after adjusting for sex, statin treatment, hypertension, diabetes, social factors and mortality (P<0.01). In contrast, serum triglyceride (TG) values increased over time in younger age groups, reached a plateau and decreased in older age groups (> 60 years at baseline). In smokers, TC, LDL-C, non-HDL-C and TG decreased less markedly than in non-smokers, while HDL-C decreased more rapidly while the LDL-C/HDL-C ratio increased. In subjects treated with lipid-lowering drugs, TC, LDL-C and non-HDL-C decreased more markedly and HDL-C less markedly than in untreated subjects while TG and LDL-C/HDL-C remained stable or increased in treatment naïve subjects. We conclude, that in this ageing population we observed marked changes in blood lipids over a 12 year follow up, with decreasing trajectories of TC, LDL-C and non-HDL-C and mixed trajectories of TG. The findings suggest that monitoring of age-related trajectories in blood lipids may improve prediction of CVD risk beyond single measurements.

• MeSH
• Cholesterol, HDL blood   MeSH
• Smoking blood   epidemiology   MeSH
• Cholesterol, LDL blood   MeSH
• Middle Aged MeSH
• Humans MeSH
• Lipids * blood   MeSH
• Longitudinal Studies MeSH
• Urban Population MeSH
• Aged MeSH
• Aging * blood   MeSH
• Triglycerides blood   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Russia epidemiology   MeSH
• Names of Substances
• Cholesterol, HDL MeSH
• Cholesterol, LDL MeSH
• Lipids * MeSH
• Triglycerides MeSH

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.

• MeSH
• Cholesterol, Dietary administration & dosage   adverse effects   MeSH
• Diet, High-Fat * adverse effects   MeSH
• Hypercholesterolemia chemically induced   genetics   metabolism   MeSH
• Liver metabolism   MeSH
• Rats MeSH
• DNA Methylation genetics   MeSH
• Rats, Wistar MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Cholesterol, Dietary MeSH

BACKGROUND: Plasma triglyceride (TG) values are significant predictors of cardiovascular and total mortality. The plasma levels of TGs have an important genetic background. We analyzed whether 32 single nucleotide polymorphisms (SNPs) identified in genome-wide association studies are discriminators of hypertriglyceridemia (HTG) in the Czech population. OBJECTIVES: The objective of this study was to replicate and test the original findings in an independent study and to re-analyze the gene score leading to HTG. METHODS: In total, we analyzed 32 SNPs in 209 patients with plasma TG levels over 10 mmol/L (HTG group) and compared them in a case-control design with 524 treatment-naïve controls (normotriglyceridemic [NTG] group) with plasma TG values below 1.8 mmol/L. RESULTS: Sixteen SNPs were significantly associated with an increased risk of HTG development, with odds ratios (ORs) (95% confidence interval [CI]) varying from 1.40 (1.01-1.95) to 4.69 (3.29-6.68) (rs964184 within the APOA5 gene). Both unweighted (sum of the risk alleles) and weighted gene scores (WGS) (log of the achieved ORs per individual genotype) were calculated, and both gene scores were significantly different between groups. The mean score of the risk alleles was significantly increased in the HTG group compared to the NTG group (18.5 ± 2.5 vs. 15.7 ± 2.3, respectively; P < 0.00001). Subjects with a WGS over 9 were significantly more common in the HTG group (44.5%) than in the NTG group, in which such a high score was observed in only 4.7% of subjects (OR 16.3, 95% CI 10.0-36.7; P < 0.0000001). CONCLUSIONS: An increased number of risk genetic variants, calculated both in a weighted or unweighted manner, significantly discriminates between the subjects with HTG and controls. Population-specific sets of SNPs included into the gene score seem to yield better discrimination power.

• MeSH
• Alleles MeSH
• Genetic Predisposition to Disease * MeSH
• Genetic Association Studies * methods   MeSH
• Genetic Testing MeSH
• Genotype MeSH
• Hypertriglyceridemia blood   diagnosis   epidemiology   genetics   MeSH
• Polymorphism, Single Nucleotide MeSH
• Comorbidity MeSH
• Middle Aged MeSH
• Humans MeSH
• Odds Ratio MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic epidemiology   MeSH

Apolipoprotein A5 (APOA5) is a small protein, expressed predominantly in the liver. In plasma, it is located on triglyceride rich lipoprotein particles (chylomicrones and VLDL) and on HDL. Plasma concentration of apolipoprotein A5 is very low, suggesting rather regulatory (activation of lipoprotein lipase, …) than structural function. APOA5 is an important determinant of plasma triglyceride concentration; this effect has been confirmed both on animal models, as well as on human studies. Minor alleles of three commonly analysed variants within this gene (rs662799, rs3135506, rs2075291) are associated with higher plasma TG values and increased risk of myocardial infarction, with some important interethnic differences observed. Further roles of APOA5; determination of BMI, diabetes and last but not least nutri- and pharmaco-genetic interactions are suggested, but without the definitive conclusions.

• Keywords
• Apolipoprotein A5, Cardiovascular disease, Polymorphism, Triglycerides,
• MeSH
• Apolipoprotein A-V blood   genetics   metabolism   MeSH
• Polymorphism, Single Nucleotide * MeSH
• Cardiovascular Diseases blood   epidemiology   genetics   MeSH
• Humans MeSH
• Triglycerides blood   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• APOA5 protein, human MeSH Browser
• Apolipoprotein A-V MeSH
• Triglycerides MeSH