Gene-diet interaction and plasma lipid responses to dietary intervention

2002 ◽  
Vol 30 (2) ◽  
pp. 68-73 ◽  
Author(s):  
J. M. Ordovas
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Successful Aging ◽  
Dietary Intervention ◽  
Dietary Habits ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Dietary Recommendations ◽  
Dietary Pufa ◽  
Increased Risk

Strategies for disease prevention can have a major impact on people's health. However, major gaps exist in our knowledge with regard to nutritional adequacy, nutrient-disease interactions, nutrient-gene interactions, and effective strategies for implementation of dietary recommendations which have the potential to decrease the disease burden and to contribute to successful aging of the population. Coronary heart disease is one of the major causes of mortality in the world. We have sound evidence that high levels of low-density lipoprotein cholesterol (LDL-C) and low levels of high-density lipoprotein cholesterol (HDL-C) are associated with increased risk of coronary heart disease. Lipoprotein concentrations are associated with environmental variables such as diet and lifestyle, but genetics also play a significant role. We have examined polymorphisms at candidate loci to determine their usefulness as markers for dietary responses. A G/A polymorphism 75 bp upstream from the gene encoding apolipoprotein AI (APOA1) has been described in ~ 30% of the population. Our studies show that this polymorphism is associated with variability in the HDL-C response to dietary fat, specifically to polyunsaturated fatty acids (PUFA) in the diet. Carriers of the A allele respond to increases in dietary PUFA with elevations in HDL-C levels, probably due to altered interactions of transcription factors with the mutated promoter. Therefore carriers of the A allele can potentially decrease their atherogenic risk by consuming high-PUFA diets. Likewise, we have examined the interaction between other dietary habits, such as alcohol drinking, and variability at the APOE locus, and have demonstrated that the classical associations between APOE polymorphism and LDL-C levels are observed primarily in those subjects who consume alcohol. Moreover, we have found a subgroup of the population, APOE4 carriers, for whom drinking alcohol may exert detrimental effects on lipid metabolism. This knowledge will contribute towards the development of more effective personalized dietary recommendations.

scholarly journals Triglyceride-containing lipoprotein sub-fractions and risk of coronary heart disease and stroke: A prospective analysis in 11,560 adults

2020 ◽  
Vol 27 (15) ◽  
pp. 1617-1626 ◽  
Author(s):  
Roshni Joshi ◽  
S Goya Wannamethee ◽  
Jorgen Engmann ◽  
Tom Gaunt ◽  
Deborah A Lawlor ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Odds Ratio ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Increased Risk ◽  
The Individual

Aims Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease; however, there is uncertainty about the role of total triglycerides and the individual triglyceride-containing lipoprotein sub-fractions. We measured 14 triglyceride-containing lipoprotein sub-fractions using nuclear magnetic resonance and examined associations with coronary heart disease and stroke. Methods Triglyceride-containing sub-fraction measures were available in 11,560 participants from the three UK cohorts free of coronary heart disease and stroke at baseline. Multivariable logistic regression was used to estimate the association of each sub-fraction with coronary heart disease and stroke expressed as the odds ratio per standard deviation increment in the corresponding measure. Results The 14 triglyceride-containing sub-fractions were positively correlated with one another and with total triglycerides, and inversely correlated with high-density lipoprotein cholesterol (HDL-C). Thirteen sub-fractions were positively associated with coronary heart disease (odds ratio in the range 1.12 to 1.22), with the effect estimates for coronary heart disease being comparable in subgroup analysis of participants with and without type 2 diabetes, and were attenuated after adjustment for HDL-C and LDL-C. There was no evidence for a clear association of any triglyceride lipoprotein sub-fraction with stroke. Conclusions Triglyceride sub-fractions are associated with increased risk of coronary heart disease but not stroke, with attenuation of effects on adjustment for HDL-C and LDL-C.

scholarly journals Association between the TIMD4-HAVCR1 variants and serum lipid levels, coronary heart disease and ischemic stroke risk and atorvastatin lipid-lowering efficacy

2018 ◽  
Vol 38 (1) ◽  
Author(s):  
Qing-Hui Zhang ◽  
Rui-Xing Yin ◽  
Wu-Xian Chen ◽  
Xiao-Li Cao ◽  
Yu-Ming Chen
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Ischemic Stroke ◽  
Serum Lipid ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Lipid Levels ◽  
Serum Lipid Levels ◽  
Increased Risk

Little is known about the association of the TIMD4 (T-cell immunoglobulin and mucin domain 4 gene)-HAVCR1 (hepatitis A virus cellular receptor 1) variants and lipid metabolism, the risk of coronary heart disease (CHD) and ischemic stroke (IS). The present study aimed to determine the TIMD4-HAVCR1 variants, their haplotypes and gene–environment interactions on serum lipid levels, the risk of CHD and IS, and the lipid-lowering efficacy of atorvastatin in a southern Chinese Han population. Genotypes of three variants in 622 controls, 579 CHD, and 546 IS patients were determined by the Snapshot technology. Atorvastatin calcium tablet (20 mg/day) was given in 724 hyperlipidemic patients for 8 weeks after genotyping. The rs12522248 genotypic and allelic frequencies were different between controls and patients, and were associated with the risk of CHD and IS. The rs1501908G-rs12522248T-rs2036402T haplotype was associated with an increased risk of CHD; the G-C-T haplotype was associated with lower risk of CHD; and the C-C-C haplotype was associated with an increased risk of IS. Variants and their haplotypes in controls were associated with triglyceride (rs1501908), low-density lipoprotein cholesterol (LDL-C, rs1501908, G-T-T), high-density lipoprotein cholesterol (HDL-C, rs12522248, C-C-C) and the ratio of total cholesterol (TC) to HDL-C (C-C-C). Interactions of rs1501908- and rs2036402-alcohol (HDL-C); rs1501908- and rs12522248-high body mass index (hBMI, ≥24 kg/m2; TC); and TIMD4-HAVCR1 variants-atorvastatin on several lipid parameters were detected. Interactions of rs12522248TC/CC-hBMI, G-T-T-, and C-C-C-smoking on the risk of CHD; and C-C-C-smoking, C-C-C-, and G-C-T-hBMI on the risk of IS were also observed. These findings suggest that the TIMD4-HAVCR1 variants may be the genetic risk factors for CHD and IS.

scholarly journals Exploring the causal pathway from body mass index to coronary heart disease: a network Mendelian randomization study

2020 ◽  
Vol 11 ◽  
pp. 204062232090904
Author(s):  
Xun Hu ◽  
Xiao-Dong Zhuang ◽  
Wei-Yi Mei ◽  
Gang Liu ◽  
Zhi-Min Du ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Causal Association ◽  
Increased Risk ◽  
Lipid Parameters

Background: We applied a network Mendelian randomization (MR) framework to determine the causal association between body mass index (BMI) and coronary heart disease (CHD) and explored whether glycated hemoglobin (HbA1c) and lipid parameters (total cholesterol, TC; low-density lipoprotein cholesterol, LDL; high-density lipoprotein cholesterol, HDL; triglycerides, TG) serve as causal mediators from BMI to CHD by integrating summary-level genome-wide association study data. Methods: Network MR analysis, an approach using genetic variants as the instrumental variables for both the exposure and mediator to infer causality was performed. Summary statistics from the GIANT consortium were used ( n = 152,893) for BMI, CARDIoGRAMplusC4D consortium data were used ( n = 184,305) for CHD, Global Lipids Genetics Consortium data were used ( n = 108,363) for TC, LDL, HDL and TG, and MAGIC consortia data were used ( n = 108,363) for HbA1c. Results: The inverse-variance-weighted-method estimate indicated that the odds ratio (95% confidence interval) for CHD was 1.562 (1.391–1.753) per 1 standard deviation (kg/m2) increase in BMI. Results were consistent in MR Egger method and weighted-median methods. MR estimate indicated that BMI was positively associated with HbA1c and TG, and negatively associated with HDL, but was not associated with TC or LDL. Moreover, HbA1c, TC, LDL, and TG were positively associated with CHD, yet there was no causal association between HDL and CHD. HbA1c was positively associated with TC, LDL, and HDL, but was not associated with TG. Conclusions: Higher BMI conferred an increased risk of CHD, which was partially mediated by HbA1c and lipid parameters. HbA1c and TG might be the main mediators in the link from BMI to CHD.

Hypercholesterolemia and Hyper-α-Lipoproteinemia in Schoolchildren

PEDIATRICS ◽  
1978 ◽  
Vol 62 (4) ◽  
pp. 478-487
Author(s):  
Charles J. Glueck ◽  
Kathe Kelly ◽  
Margot J. Mellies ◽  
Peter S. Gartside ◽  
Paula M. Steiner
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
High Density Lipoprotein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Increased Risk ◽  
Reduced Risk

Elevated levels of high-density lipoprotein cholesterol (C-HDL) can explain apparent hypercholesterolemia in some children, and high C-HDL levels may aggregate in families. In this study, 17 kindreds were identified by virtue of hypercholesterolemic proband children whose hypercholesterolemia was accounted for by elevated C-HDL levels. Family lipid and lipoprotein sampling revealed three-generation vertical appearance of elevated C-HDL level in two kindreds, and two-generation vertical appearance in eight additional kindreds. Since C-HDL level is inversely associated with coronary heart disease in adults, it is important to quantitate C-HDL and low-density lipoprotein cholesterol (C-LDL) in hypercholesterolemic children and to identify those with putatively reduced risk (elevated C-HDL level) or increased risk (elevated C-LDL level).

scholarly journals Risk factors for coronary heart disease and actual diagnostic criteria for diabetes mellitus

2009 ◽  
Vol 66 (12) ◽  
pp. 973-978 ◽  
Author(s):  
Natasa Mitrovic-Perisic ◽  
Slobodan Antic
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Glucose Tolerance ◽  
Diagnostic Criteria ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Chronic Hyperglycemia ◽  
Increased Risk

Background/Aim. Recent studies indicate that the prevalence of diabetes mellitus (DM) type 2 is increasing in the world. Chronic hyperglycemia in DM is associated with a long term damage, dysfunction and failure of various organs, especially retina, kidney, nerves and, in addition, with an increased risk of cardiovasclar disease. For a long time the illness has been unknown. Early diagnosis of diabetes could suspend the development of diabetic complications. The aim of the study was to establish risk for the development of coronary disease in the patients evaluated by the use of new diagnostic criteria for DM. Methods. The study included 930 participants without diagnosis of DM, hypertension, dyslipidemia, nor coronary heart disease two years before the study. The patients went through measuring of fasting plasma glycemia, erythrocytes, hematocrit, cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, aspartate aminotransferase and alanine aminotransferase. In the group with hyperglycemia the 2-hour oral glucose tolerance test was performed. We analyzed ECG and made blood pressure monitoring, and also measured body mass, height, waist and hip circumference. We analyzed life style, especially smoking, and exercise and family history. Results. Diabetes prevalence was 2.68%, and prevalences of impaired fasting glucose, impaired glucose tolerance and DM were 12.15%. Average age of males and females was 38 and 45 years, respectively. In the healthy population there was higher frequency of smokers (55% vs 42%), but in the population with hyperglycemia there were more obesity (23% vs 10.5%), hypertension (39% vs 9%), hypercholesterolemia (76% vs 44.1%), lower HDL-C (52.2% vs 25.7%). Cummulative risk factor in healthy subjects, and those with hyperglycemia were 5.6% and 14%, respectively. Conclusion. Subjects with hyperglicemia without diagnosis of DM have higher risk factors for coronary heart disease.

scholarly journals Isolated Low Levels of High-Density Lipoprotein Cholesterol Are Associated With an Increased Risk of Coronary Heart Disease

Circulation ◽  
2011 ◽  
Vol 124 (19) ◽  
pp. 2056-2064 ◽  
Author(s):  
Rachel R. Huxley ◽  
Federica Barzi ◽  
Tai Hing Lam ◽  
Sebastien Czernichow ◽  
Xianghua Fang ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Increased Risk ◽  
Low Levels

scholarly journals Joint association between education and polygenic risk score for incident coronary heart disease events: a longitudinal population-based study of 26 203 men and women

2021 ◽  
pp. jech-2020-214358
Author(s):  
Pekka Martikainen ◽  
Kaarina Korhonen ◽  
Aline Jelenkovic ◽  
Hannu Lahtinen ◽  
Aki Havulinna ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Risk Score ◽  
Density Lipoprotein ◽  
Population Based ◽  
Polygenic Risk Score ◽  
Genome Wide ◽  
Increased Risk ◽  
Region Of Residence

BackgroundGenetic vulnerability to coronary heart disease (CHD) is well established, but little is known whether these effects are mediated or modified by equally well-established social determinants of CHD. We estimate the joint associations of the polygenetic risk score (PRS) for CHD and education on CHD events.MethodsThe data are from the 1992, 1997, 2002, 2007 and 2012 surveys of the population-based FINRISK Study including measures of social, behavioural and metabolic factors and genome-wide genotypes (N=26 203). Follow-up of fatal and non-fatal incident CHD events (N=2063) was based on nationwide registers.ResultsAllowing for age, sex, study year, region of residence, study batch and principal components, those in the highest quartile of PRS for CHD had strongly increased risk of CHD events compared with the lowest quartile (HR=2.26; 95% CI: 1.97 to 2.59); associations were also observed for low education (HR=1.58; 95% CI: 1.32 to 1.89). These effects were largely independent of each other. Adjustment for baseline smoking, alcohol use, body mass index, igh-density lipoprotein (HDL) and total cholesterol, blood pressure and diabetes attenuated the PRS associations by 10% and the education associations by 50%. We do not find strong evidence of interactions between PRS and education.ConclusionsPRS and education predict CHD events, and these associations are independent of each other. Both can improve CHD prediction beyond behavioural risks. The results imply that observational studies that do not have information on genetic risk factors for CHD do not provide confounded estimates for the association between education and CHD.

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