title: Cholesteryl ester transfer protein polymorphism (TaqIB) associates with risk in postinfarction patients with high C-reactive protein and high-density lipoprotein cholesterol levels.
abstract: OBJECTIVE
  To investigate the roles of inflammation and a cholesteryl ester transfer protein (CETP) polymorphism potentially related to recent findings demonstrating coronary risk with increasing high-density lipoprotein cholesterol (HDL-C) level.
  
  
  RESULTS
  A novel graphical exploratory data analysis tool allowed the examination of coronary risk in postinfarction patients relating to HDL-C and C-reactive protein levels. Results demonstrated a high-risk subgroup, defined by high HDL-C and C-reactive protein levels, exhibiting larger HDL particles and lower lipoprotein-associated phospholipaseA(2) levels than lower-risk patients. Subgroup CETP-associated risk was probed using a functional CETP polymorphism (TaqIB, rs708272). In the high-risk subgroup, multivariable modeling revealed greater risk for B2 allele carriers (less CETP activity) versus B1 homozygotes (hazard ratio, 2.41; 95% CI, 1.04 to 5.60; P=0.04). Within the high-risk subgroup, B2 allele carriers had higher serum amyloid A levels than B1 homozygotes. Evidence also demonstrates that CETP genotypic differences in HDL subfraction distributions regarding non-HDL-C and lipoprotein-associated phospholipaseA(2) may potentially relate to impaired HDL remodeling.
  
  
  CONCLUSIONS
  Postinfarction patients with high HDL-C and C-reactive protein levels demonstrate increased risk for recurrent events. Future studies should aim at characterizing altered HDL particles from such patients and at elucidating the mechanistic details related to inflammation and HDL particle remodeling. Such patients should be considered in drug trials involving an increase in HDL-C level.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY 14642, USA. James_Corsetti@urmc.rochester.edu
authors.forename: James P
authors.initials: JP
authors.lastname: Corsetti
authors.forename: Dan
authors.initials: D
authors.lastname: Ryan
authors.forename: David L
authors.initials: DL
authors.lastname: Rainwater
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zareba
authors.forename: Charles E
authors.initials: CE
authors.lastname: Sparks
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D016009:Chi-Square Distribution; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood*; D003327:Coronary Disease / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000401:mortality; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000401:mortality; D010641:Phenotype; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D000685:Serum Amyloid A Protein / Q000032:analysis; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D000685:Serum Amyloid A Protein; D002097:C-Reactive Protein; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase