title: The contribution of a 9p21.3 variant, a KIF6 variant, and C-reactive protein to predicting risk of myocardial infarction in a prospective study.
abstract: BACKGROUND
  Genetic risk factors might improve prediction of coronary events. Several variants at chromosome 9p21.3 have been widely reported to be associated with coronary heart disease (CHD) in prospective and case-control studies. A variant of KIF6 (719Arg) has also been reported to be associated with increased risk of CHD in large prospective studies, but not in case-control studies. We asked whether the addition of genetic information (the 9p21.3 or KIF6 variants) or a well-established non-genetic risk factor (C-reactive protein [CRP]) can improve risk prediction by the Framingham Risk Score (FRS) in the Cardiovascular Health Study (CHS)--a prospective observational study of risk factors for cardiovascular disease among > 5,000 participants aged 65 or older.
  
  
  METHODS
  Improvement of risk prediction was assessed by change in the area under the receiver-operator characteristic curve (AUC) and by net reclassification improvement (NRI).
  
  
  RESULTS
  Among white participants the FRS was improved by addition of KIF6 719Arg carrier status among men as assessed by the AUC (from 0.581 to 0.596, P = 0.03) but not by NRI (NRI = 0.027, P = 0.32). Adding both CRP and 719Arg carrier status to the FRS improved risk prediction by the AUC (0.608, P = 0.02) and NRI (0.093, P = 0.008) in men, but not women (P ≥ 0.24).
  
  
  CONCLUSIONS
  While none of these risk markers individually or in combination improved risk prediction among women, a combination of KIF6 719Arg carrier status and CRP levels modestly improved risk prediction among white men; although this improvement is not significant after multiple-testing correction. These observations should be investigated in other prospective studies.
authors.affiliation: Celera, 1401 Harbor Bay Parkway, Alameda, CA 94502 USA. dov.shiffman@celera.com
authors.forename: Dov
authors.initials: D
authors.lastname: Shiffman
authors.forename: Ellen S
authors.initials: ES
authors.lastname: O'Meara
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rowland
authors.forename: Judy Z
authors.initials: JZ
authors.lastname: Louie
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.forename: James J
authors.initials: JJ
authors.lastname: Devlin
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D044383:Black People / Q000235:genetics; D002097:C-Reactive Protein / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D016547:Kinesins / Q000235:genetics*; D008297:Male; D009203:Myocardial Infarction / Q000175:diagnosis* / Q000235:genetics*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D002097:C-Reactive Protein; C526774:KIF6 protein, human; D016547:Kinesins