title: Analysis of gene-environment interaction in coronary artery disease: lipoprotein lipase and smoking as examples.
abstract: 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.
authors.affiliation: Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free and University College London Medical School, UK. rmhapjt@ucl.ac.uk
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Talmud
authors.forename: Emma
authors.initials: E
authors.lastname: Hawe
authors.forename: George J
authors.initials: GJ
authors.lastname: Miller
mesh_terms: D003324:Coronary Artery Disease / Q000209:etiology / Q000235:genetics*; D004781:Environmental Exposure; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008967:Molecular Biology; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000503:physiopathology
chemical_list: D008071:Lipoprotein Lipase