Background: A widely held hypothesis is that interactions between genetic predisposition and Western-type lifestyle contribute to the epidemic of type 2 diabetes (T2D). No study has tested this hypothesis.
Objective: The objective was to assess whether established genetic variants, mainly from genomewide association studies, modify dietary patterns in predicting diabetes risk.
Design: We determined 10 polymorphisms in a prospective, nested, case-control study of 1196 diabetic and 1337 nondiabetic men. A genetic risk score (GRS) was generated by using an allele counting method. Baseline dietary intakes were collected by using a semiquantitative food-frequency questionnaire. We used factor analysis to derive Western and "Prudent" dietary patterns from 40 food groups.
Results: A significant interaction (P = 0.02) was observed between the GRS and Western dietary pattern. The multivariable odds ratios (ORs) of T2D across increasing quartiles for the Western dietary pattern were 1.00, 1.23 (95% CI: 0.88, 1.73), 1.49 (1.06,2.09), and 2.06 (1.48, 2.88) among men with a high GRS (>/=12 risk alleles; P for trend = 0.01). The Western dietary pattern was not associated with diabetes risk among those with a lower GRS. In addition, we found that intakes of processed meat, red meat, and heme iron, which characterized the Western dietary pattern, showed significant interactions with GRS in relation to diabetes risk (P for interaction = 0.029, 0.02, and 0.0004, respectively). The diet-diabetes associations were more evident among men with a high GRS (>/=12) than in those with a low GRS.
Conclusion: Genetic predisposition may synergistically interact with a Western dietary pattern in determining diabetes risk in men.