Robert Y L Zee1, Hillary H Hegener, Jessica Gould, Paul M Ridker. 1. Center for Cardiovascular Disease Prevention, and the Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass 02215, USA. rzee@rics.bwh.harvard.edu
Abstract
BACKGROUND AND PURPOSE: Recent findings of an association between a functional toll-like receptor 4 (TLR4) D299G gene variant and reduced risk of atherothrombotic disorders have generated great interest. METHODS: We evaluated the TLR4 D299G polymorphism among 695 individuals with incident myocardial infarction (MI) or stroke and among 695 age- and smoking-matched individuals who remained free of reported cardiovascular disease during follow-up within the Physicians' Health Study. RESULTS: Overall, we observed little evidence of association between the D299G polymorphism and risk of any atherothrombotic event (P=0.25), incident MI (P=0.89), or stroke (P=0.09), assuming an additive model. Adjusting for traditional cardiovascular risk factors or assuming a dominant model yielded similar null findings. Whereas the observed carrier frequency of the D299G polymorphism in our data (13.0%) is consistent with those observed in most other studies, it was higher than the 6.8% carrier frequency observed in the initial study that suggested a protective effect for this gene variant. Thus, this former association may have been caused, in part, by an underestimation of the control frequency. CONCLUSIONS: In contrast to previous data, the D299G TLR4 polymorphism was not associated with risk of incident MI or stroke in this large prospective study of US men.
BACKGROUND AND PURPOSE: Recent findings of an association between a functional toll-like receptor 4 (TLR4) D299G gene variant and reduced risk of atherothrombotic disorders have generated great interest. METHODS: We evaluated the TLR4D299G polymorphism among 695 individuals with incident myocardial infarction (MI) or stroke and among 695 age- and smoking-matched individuals who remained free of reported cardiovascular disease during follow-up within the Physicians' Health Study. RESULTS: Overall, we observed little evidence of association between the D299G polymorphism and risk of any atherothrombotic event (P=0.25), incident MI (P=0.89), or stroke (P=0.09), assuming an additive model. Adjusting for traditional cardiovascular risk factors or assuming a dominant model yielded similar null findings. Whereas the observed carrier frequency of the D299G polymorphism in our data (13.0%) is consistent with those observed in most other studies, it was higher than the 6.8% carrier frequency observed in the initial study that suggested a protective effect for this gene variant. Thus, this former association may have been caused, in part, by an underestimation of the control frequency. CONCLUSIONS: In contrast to previous data, the D299GTLR4 polymorphism was not associated with risk of incident MI or stroke in this large prospective study of US men.
Authors: Daniel A Enquobahrie; Nicholas L Smith; Joshua C Bis; Cara L Carty; Kenneth M Rice; Thomas Lumley; Lucia A Hindorff; Rozenn N Lemaitre; Michelle A Williams; David S Siscovick; Susan R Heckbert; Bruce M Psaty Journal: Am J Cardiol Date: 2008-04-09 Impact factor: 2.778
Authors: Yeun Sun Kim; You Jin Hwang; Sung Yong Kim; Sun Mee Yang; Ki Young Lee; Ie Byung Park Journal: Yonsei Med J Date: 2008-02-29 Impact factor: 2.759