Abstract

Background: Studies have found associations between genetic polymorphisms, food intake, physical activity, body mass index, and metabolic syndrome (METs). Objective: We hypothesized that a genetic risk score (GRS) with food intake and physical activity are influenced by mediational and interaction effects to increase METs among White and African American adults. Methods: We used the Atherosclerosis Risk In Communities (ARIC) study data at the third visit from 1996-1998. Data included 8,416 Whites and 2,061 African Americans aged 41-71y with 1,484 and 517 cases of METs, respectively. METs was defined according to the International Diabetes Federation criteria. Dietary data were obtained from the ARIC study food frequency questionnaire. The GRS was composed of eight single nucleotide polymorphisms involved in cardiovascular and lipid metabolism, known to have defects in protein binding and function. Mediational path analysis using linear-and-logistic regression was used to test simultaneous associations, and interaction using multivariate logistic regression tested relationships between the GRS, food intake, physical activity and METs. In mediational path analysis, Root Mean Square Error of Approximation, p>0.05, Comparative Factor Index, p>0.90, Tucker-Lewis Index, p>0.90, and chi-square test, p>0.05 were used to assess statistical significance. For interaction using logistic regression analysis, odds ratios (OR) and 95% confidence intervals with p<0.05 were used to judge statistical significance. Results: In multivariate logistic regression, the GRS was associated with a 22% increased risk for METs among Whites (OR=1.22; 1.03-1.44), while this association was not significant in African Americans. After adjustment for Bonferonni correction for mass significance (p<0.001), we found among Whites that energy-adjusted total fat, animal fat, caloric intake, sugar-sweetened drinks, red meat, fried foods, and processed meats were associated with higher risk for METs, while energy-adjusted total carbohydrates, crude fiber, dietary fiber, and cereal fiber had a protective association with METs. These results were similar in African Americans but did not meet Bonferonni significance. In mediational analysis, we observed insignificant mediational effects, but significant direct effects for the GRS to METs for physical activity (OR=1.164; p=0.047) and fish intake (OR=1.161; p=0.050) among Whites and for carbohydrate intake (OR=1.164; p=0.058) and drinks consumed (OR=4.445; p<0.0000) among overweight/obese Whites. In interaction models, energy-adjusted carbohydrate, protein, animal fat, fructose, and sugary drinks interacted with the GRS to affect METs among Whites, but not African Americans. Conclusion: A GRS operates through interaction with dietary factors and physical activity rather than by their mediational effects on METs among White adults.

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