Biomedical subjects

Philippa J Talmud

Publications and source records attributed to Philippa J Talmud.

41 records · Page 3Linked to original sources

PubMed2002

Nonfasting apolipoprotein B and triglyceride levels as a useful predictor of coronary heart disease risk in middle-aged UK men.

OBJECTIVE: The Apolipoprotein-related Mortality Risk (AMORIS) study concluded that the apolipoprotein (apo)B/apoA-I ratio was the best predictor of coronary heart disease (CHD) risk. We have compared the pairwise combinations of total cholesterol, triglycerides (TGs), apoB, high density lipoprotein (HDL) cholesterol, low density lipoprotein cholesterol, and apoA-I on CHD risk prediction in middle-aged men. METHODS AND RESULTS: Healthy middle-aged men (n=2508), free of CHD at baseline, were examined prospectively. Over 6 years of follow-up, there were 163 CHD events (including acute myocardial infarction, coronary artery surgery, and ECG evidence of silent myocardial infarction). The relative risk (RR) of CHD associated with cholesterol, TGs, apoB, apoA-I, apoB/apoA-I, low density lipoprotein cholesterol, and HDL cholesterol were examined by survival analysis. The apoB/apoA-I ratio was associated with the strongest effect on the RR (3.58, 95% CI 2.08 to 6.19). In multivariate analysis, apoA-I had no significant effect on risk. Examining RR by quartiles, apoB and HDL in combination (RR 8.38, 95% CI 3.21 to 21.92) were better predictors of CHD risk than apoB and TGs (RR 4.05, 95% CI 1.57 to 6.23). However, apoB and TGs in combination added risk information over and above lifestyle factors, whereas apoB and HDL cholesterol did not. CONCLUSIONS: The combined evaluation of apoB with TGs provides useful diagnostic criteria for CHD risk.

Apolipoproteins B↗

PubMed2002

Peroxisome proliferator-activated receptor alpha gene variants influence progression of coronary atherosclerosis and risk of coronary artery disease.

BACKGROUND: Peroxisome proliferator-activated receptor alpha (PPARalpha) regulates the expression of genes involved in lipid metabolism and inflammation, making it a candidate gene for atherosclerosis and ischemic heart disease (IHD). METHODS AND RESULTS: We investigated the association between the leucine 162 to valine (L162V) polymorphism and a G to C transversion in intron 7 of the PPARalpha gene and progression of atherosclerosis in the Lopid Coronary Angiography Trial (LOCAT), a trial examining the effect of gemfibrozil treatment on progression of atherosclerosis after bypass surgery and on risk of IHD in the second Northwick Park Heart Study (NPHS2), a prospective study of healthy middle-aged men in the United Kingdom. There was no association with plasma lipid concentrations in either study. Both polymorphisms influenced progression of atherosclerosis and risk of IHD. V162 allele carriers had less progression of diffuse atherosclerosis than did L162 allele homozygotes with a similar trend for focal atherosclerosis. Intron 7 C allele carriers had greater progression of atherosclerosis than did G allele homozygotes. The V162 allele attenuated the proatherosclerotic effect of the intron 7 C allele. Homozygotes for the intron 7 C allele had increased risk of IHD, an effect modulated by the L162V polymorphism CONCLUSIONS: The PPARalpha gene affects progression of atherosclerosis and risk of IHD. Absence of association with plasma lipid concentrations suggests that PPARalpha affects atherosclerotic progression directly in the vessel wall.

Aged↗

PubMed2002

Gene:environment interaction in lipid metabolism and effect on coronary heart disease risk.

Both genetic and environmental factors influence coronary heart disease, therefore studies of coronary heart disease risk are often confounded by gene:gene and gene:environment interactions. Such interactions imply that at the molecular level there is synergy between the gene products or with the by-products of the environmental insult, resulting in a greater than additive effect on risk. Genetic risk is thus modifiable in an environment-specific manner. This review focuses on recently reported effects of smoking (environmental factor) on the impact of variation in the genes for glutathione S-transferase, paraoxonase and apolipoprotein E on the risk of coronary heart disease and effects on intermediate lipid traits. We end on a cautionary note for the need for repeat studies to confirm these reported gene:environment effects.

Apolipoproteins E↗

PubMed2002

Analysis of gene-environment interaction in coronary artery disease: lipoprotein lipase and smoking as examples.

In a complex disorder such as coronary artery disease (CAD), both genetic and environmental factors influence the onset of disease. Such interactions imply that at the molecular level there is interplay between the gene product and the environmental insult, resulting in a greater than additive effect on risk; for example the synergy between variation in the lipoprotein lipase (LPL) gene and smoking on risk. LPL plays a dual role in lipid metabolism both in the hydrolysis of triglyceride-rich lipoproteins and also as a molecular bridge, enhancing the receptor-mediated uptake of lipoproteins both by the liver (anti-atherogenic) but also by receptors on the artery wall (pro-atherogenic). Smoking is associated with a 2-fold increase in CAD risk, and the mechanisms for this include endothelial damage and promotion of lipid oxidation. Results from a prospective study on CAD risk in healthy middle-aged men show that the risk associated with the LPL-D9N variant, which has a modest effect on plasma triglyceride levels, is enhanced up to 10 fold, but only in men who smoke. The proposed mechanism for this LPL:smoking interaction on CAD risk is the subject of this review.

Coronary Artery Disease↗

PubMed2002

Dietary long-chain n-3 PUFAs increase LPL gene expression in adipose tissue of subjects with an atherogenic lipoprotein phenotype.

We sought to test the hypothesis that dietary long-chain n-3 PUFA (LC n-3 PUFA) in fish oil stimulate the gene expression of lipoprotein lipase (LPL) in human adipose tissue (AT). In a randomized, double blind, placebo-controlled, cross-over study, 51 male subjects expressing an atherogenic lipoprotein phenotype (ALP) had their diets supplemented with fish oil for 6 weeks. As we previously reported for this group, supplementation with LC n-3 PUFA produced a decrease in fasting plasma triglyceride (TG) (-35%, P < 0.05), attenuation of the postprandial TG response (area and incremental area under the curve; AUC and IAUC, P < 0.05), and a decrease in small, dense LDL. The present study extended these observations by showing that these changes were accompanied by a marked increase in the concentration of LPL mRNA in adipose tissue (AT-LPL mRNA, +55%, P = 0.003) and post-heparin LPL activity (PH-LPL, +31%, P = 0.036). There was also evidence of an association between LPL gene expression and polymorphism in the apolipoprotein E gene. We conclude that the favorable influence of dietary n-3 PUFA on the ALP may be mediated, in part, through an increase in the plasma activity and gene expression of lipoprotein lipase in human adipose tissue.

Adipose Tissue↗