title: Genetic effects on postprandial variations of inflammatory markers in healthy individuals.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA. ycheng@medicine.umaryland.edu
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Cheng
authors.forename: Wen-Hong L
authors.initials: WH
authors.lastname: Kao
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
authors.forename: A Richey
authors.initials: AR
authors.lastname: Sharrett
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Ryan
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vogel
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shuldiner
authors.forename: Toni I
authors.initials: TI
authors.lastname: Pollin
mesh_terms: D000328:Adult; D000886:Anthropometry; D015415:Biomarkers; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D004041:Dietary Fats / Q000008:administration & dosage*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D019518:Postprandial Period / Q000235:genetics*; D033303:Protestantism; D012016:Reference Values; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D004041:Dietary Fats; D053583:Interleukin-1beta; D002097:C-Reactive Protein; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1