Robert Y L Zee1, Hooman Hennessey, Sherri E Michaud, Paul M Ridker. 1. Center for Cardiovascular Disease Prevention, The Donald W. Reynolds Center for Cardiovascular Research, The Leducq Center for Molecular and Genetic Epidemiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 022215, USA. rzee@rics.bwh.harvard.edu
Abstract
BACKGROUND AND PURPOSE: Recent findings implicating specific gene polymorphisms of the interleukin-1 superfamily gene cluster in the risk of developing athero-thrombotic disorders have generated great interest. However, to date, no prospective, genetic-epidemiological data are available. METHODS: Using DNA samples collected at baseline in a prospective cohort of 14,916 initially healthy American men, we evaluated seven gene polymorphisms within the interleukin-1 gene cluster among 599 individuals who subsequently developed athero-thrombotic event and among 599 age- and smoking-matched individuals who remained free of reported cardiovascular disease during follow-up (341 incident myocardial infarction matched case-control pairs and 258 incident ischemic stroke matched case-control pairs). RESULTS: Overall, we observed little evidence of association between the polymorphisms tested and risk of incident athero-thrombotic events. Further adjustment for traditional cardiovascular risk factors yielded similar null findings. Of note, a modest association of rs1143623 with reduced risk of incident MI was found (recessive model: OR=0.455, 95% CI=0.215-0.960, uncorrected p=0.039). However, this finding was not corrected for multiple testing, and thus requires cautious interpretation. CONCLUSION: In contrast to prior retrospective studies, our prospective data suggest that the IL-1 cluster gene variation is not associated with risk of athero-thrombotic disorders.
BACKGROUND AND PURPOSE: Recent findings implicating specific gene polymorphisms of the interleukin-1 superfamily gene cluster in the risk of developing athero-thrombotic disorders have generated great interest. However, to date, no prospective, genetic-epidemiological data are available. METHODS: Using DNA samples collected at baseline in a prospective cohort of 14,916 initially healthy American men, we evaluated seven gene polymorphisms within the interleukin-1 gene cluster among 599 individuals who subsequently developed athero-thrombotic event and among 599 age- and smoking-matched individuals who remained free of reported cardiovascular disease during follow-up (341 incident myocardial infarction matched case-control pairs and 258 incident ischemic stroke matched case-control pairs). RESULTS: Overall, we observed little evidence of association between the polymorphisms tested and risk of incident athero-thrombotic events. Further adjustment for traditional cardiovascular risk factors yielded similar null findings. Of note, a modest association of rs1143623 with reduced risk of incident MI was found (recessive model: OR=0.455, 95% CI=0.215-0.960, uncorrected p=0.039). However, this finding was not corrected for multiple testing, and thus requires cautious interpretation. CONCLUSION: In contrast to prior retrospective studies, our prospective data suggest that the IL-1 cluster gene variation is not associated with risk of athero-thrombotic disorders.
Authors: Torgun Waehre; Arne Yndestad; Camilla Smith; Terje Haug; Siv Haugen Tunheim; Lars Gullestad; Stig S Frøland; Anne G Semb; Pål Aukrust; Jan K Damås Journal: Circulation Date: 2004-03-29 Impact factor: 29.690
Authors: L Iacoviello; A Di Castelnuovo; M Gattone; A Pezzini; D Assanelli; R Lorenzet; E Del Zotto; M Colombo; E Napoleone; C Amore; A D'Orazio; A Padovani; G de Gaetano; P Giannuzzi; M B Donati Journal: Arterioscler Thromb Vasc Biol Date: 2004-11-11 Impact factor: 8.311