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Evidence is building from epidemiological and laboratory investigations to support the hypothesis that genetic variation can modulate the effect of dietary intake on metabolic parameters to promote atherosclerosis and increase the incidence of coronary heart disease (CHD). Technological advances in molecular and nutritional epidemiology now make it possible to study gene-diet interactions and CHD in human populations at a new level of sophistication. The overall goal of this project is to carry out a population-based case-control study in 2,150 cases of myocardial infarction and 2,150 matched controls from Costa Rica, to test specific hypotheses relating gene-diet induced atherosclerosis susceptibility (GDAS) markers to CHD. Twelve GDAS markers were selected for this study. GDAS markers are defined as common genetic variants that modulate the effect of intake of specific fatty acids, tocopherols, and carotenoids on atherosclerosis. We will determine whether carriers of the GDAS marker variants are at increased risk of CHD compared to wild type homozygotes when exposed to high intakes of lauric 12:0, myristic 14:0, and palmitic 16:0, and trans fatty acids particularly 18:2 trans from partially hydrogenated soybean oil. We will study whether high intakes of alpha-linolenic acid, vitamin E, carotene, particularly alpha- carotene, lutein, and lycopene reduce the risk of CHD, and whether the GDAS marker variants alleles lessen this protective effect. In secondary analyses, we will test the hypotheses that the GDAS variant alleles influence the effect of dietary fiber, cholesterol, physical activity, and smoking on CHD. Haplotypes of metabolically related GDAS markers that are better predictors of CHD than individual markers alone will be established, and for each haplotype, we will determine specific adverse dietary patterns. Dietary exposure variables will be evaluated by simultaneous analyses of a semi-quantitative food frequency questionnaire, and biochemical measures of intake including adipose tissue tocopherols and carotenoids by HPLC, and fatty acids, including trans isomers of partially hydrogenated soybean oil by GC. This study will provide the most complete data set to study numerous hypotheses relating genes, diet, and CHD, and could lead to specific targeted interventions for reducing the development of CHD.

Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.