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Quantitative trait locus determining dietary macronutrient intakes is located on human chromosome 2p22^1,2,3

¹ From the Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX

Background: Obesity is generally accompanied by increased food intake.

Objective: We sought to identify the genes influencing variation in dietary macronutrient intakes in Mexican Americans.

Design: We conducted a genome-wide scan by using data derived from food-frequency questionnaires in 816 participants from the San Antonio Family Heart Study. Household effect was simultaneously estimated in a variance component model with the use of SOLAR.

Results: All dietary intake measures (total calories, proteins, fat, saturated fat, monounsaturated fat, polyunsaturated fat, carbohydrates, and sucrose) were moderately heritable. Household effect was insignificant except on total calories and sucrose. Suggestive evidence of linkage with saturated fat intake was found on chromosome 2p22 near marker D2S1346 [logarithm of odds (LOD) = 2.62]. Intakes of total calories, fat, protein, and monounsaturated fat were also suggestively linked to the same marker. A significant linkage signal on chromosome 2p22 for leptin concentrations and fat mass was localized in this population, so we used leptin or fat mass as a covariate. Multipoint LOD scores for saturated fat dropped to 1.27 and 1.90, respectively, which suggested that this region on chromosome 2p contributes to both saturated fat intake and body adiposity. This chromosomal region contains the proopiomelanocortin gene (POMC). However, 2 polymorphisms in exon 3 of the POMC gene showed no association with saturated fat intake.

Conclusions: The results strengthen the hypothesis that chromosome 2p22 harbors genes that influence a variety of obesity-related phenotypes, including macronutrient intakes.

Key Words: Genome scan • dietary intake • obesity • POMC gene • multipoint linkage • polymorphism

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