title: LPL polymorphism (D9N) predicts cardiovascular disease risk directly and through interaction with CETP polymorphism (TaqIB) in women with high HDL cholesterol and CRP.
abstract: OBJECTIVE
  We sought to determine whether concurrently high levels of HDL cholesterol and CRP predict initial cardiovascular events in women, and to assess additional risk involving two genes encoding proteins involved in reverse cholesterol transport.
  
  
  METHODS
  A graphical approach identified high-risk subgroups in a population-based female cohort. Polymorphism-associated risk was assessed for CETP (TaqIB [rs708272]) and LPL (D9N [rs1801177]) using multivariable analysis adjusted for clinical parameters and biomarkers.
  
  
  RESULTS
  A high HDL-C/high CRP high-risk subgroup was identified. Multivariable modeling revealed D9N as predicting subgroup cardiovascular disease risk directly (minor allele-carriers versus major allele homozygotes: HR 5.16, 95% CI 1.43-18.54, p = 0.012) and through interaction with TaqIB (highest risk in minor allele carriers of both polymorphisms).
  
  
  CONCLUSIONS
  In women with high HDL-C and high CRP levels, an LPL polymorphism associated with risk and interacted with a CETP polymorphism such that the highest risk occurred in subjects with presumably decreased activities of both proteins.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. James Corsetti@urmc.rochester.edu
authors.forename: James P
authors.initials: JP
authors.lastname: Corsetti
authors.forename: Ron T
authors.initials: RT
authors.lastname: Gansevoort
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.forename: Charles E
authors.initials: CE
authors.lastname: Sparks
authors.forename: Robin P F
authors.initials: RP
authors.lastname: Dullaart
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000097:blood / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D016009:Chi-Square Distribution; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D053208:Kaplan-Meier Estimate; D008071:Lipoprotein Lipase / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D010641:Phenotype; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D002097:C-Reactive Protein; C548261:LPL protein, human; D008071:Lipoprotein Lipase