Genetic effects on postprandial variations of inflammatory markers in healthy individuals.

Circulating levels of inflammatory markers predict the risk of cardiovascular disease (CVD), mediated perhaps in part by dietary fat intake, through mechanisms only partially understood. To evaluate post-fat load changes in inflammatory markers and genetic influences on these changes, we administered a standardized high-fat meal to 838 related Amish subjects as part of the Heredity and Phenotype Intervention (HAPI) Heart Study and measured a panel of inflammatory markers, including C-reactive protein (CRP), interleukin-1beta (IL-1beta), matrix metalloproteinase-1 and -9 (MMP-1 and MMP-9), and white blood cell (WBC) count, before and 4 h after fat challenge (CRP prechallenge only). Heritabilities (h(2) +/- s.d.) of basal inflammatory levels ranged from 16 +/- 8% for MMP-9 (P = 0.02) to 90 +/- 7% for MMP-1 (P < 0.0001). Post-fat load, circulating levels of WBC, MMP-1, and MMP-9 increased by 16, 32, and 43% (all P < 0.0001), with no significant changes in IL-1beta. Postprandial changes over the 4-h period were modestly heritable for WBC (age- and sex-adjusted h(2) = 14 +/- 9%, P = 0.04), but the larger MMP-1 and MMP-9 changes appeared to be independent of additive genetic effects. These results reveal that a high-fat meal induces a considerable inflammatory response. Genetic factors appear to play a significant role influencing basal inflammatory levels but to have minimal influence on post-fat intake inflammatory changes.