Robert Y L Zee1, David Bates, Paul M Ridker. 1. Center for Cardiovascular Disease Prevention, 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: Genetic polymorphisms of the CD14 lipopolysaccharide receptor gene (CD14) and the CD18 leukocyte adhesion molecule gene (CD18) have recently been hypothesized to be risk factors for atherothrombosis. However, no prospective data on subsequent risk of stroke are available. The present investigation was conducted to examine the possible association between the CD14 C(-260)T and CD18 codon 441 gene polymorphisms and the incidence of stroke in a large, prospective, matched case-control sample from the Physicians' Health Study. METHODS: In the Physicians' Health Study, 14 916 apparently healthy men were followed over a 12-year period for stroke. Using a nested case-control study design, 338 study participants who developed stroke (cases) and 338 age- and smoking-matched study participants who remained free of reported disease during follow-up (controls) were evaluated. Both polymorphisms were determined by polymerase chain reaction with subsequent and respective restriction fragment length polymorphism gel electrophoresis. RESULTS: All observed genotype frequencies were in Hardy-Weinberg equilibrium. The allele and genotype distributions of the polymorphisms tested were similar among cases and controls, such that the relative risk of future stroke was 0.87 for CD14 C(-260)T (95% CI=0.69 to 1.11; P=0.27) and 0.99 for CD18 codon 441 (95% CI=0.77 to 1.28; P=0.96) assuming an additive mode of inheritance. No evidence of association was observed assuming dominant or recessive model, and similar null results were observed in subgroup analysis restricted to thromboembolic events CONCLUSIONS: In this large, prospective study, we found little evidence that the two previously described polymorphisms in the CD14 and CD18 genes are associated with risks of future stroke.
BACKGROUND AND PURPOSE: Genetic polymorphisms of the CD14 lipopolysaccharide receptor gene (CD14) and the CD18 leukocyte adhesion molecule gene (CD18) have recently been hypothesized to be risk factors for atherothrombosis. However, no prospective data on subsequent risk of stroke are available. The present investigation was conducted to examine the possible association between the CD14 C(-260)T and CD18 codon 441 gene polymorphisms and the incidence of stroke in a large, prospective, matched case-control sample from the Physicians' Health Study. METHODS: In the Physicians' Health Study, 14 916 apparently healthy men were followed over a 12-year period for stroke. Using a nested case-control study design, 338 study participants who developed stroke (cases) and 338 age- and smoking-matched study participants who remained free of reported disease during follow-up (controls) were evaluated. Both polymorphisms were determined by polymerase chain reaction with subsequent and respective restriction fragment length polymorphism gel electrophoresis. RESULTS: All observed genotype frequencies were in Hardy-Weinberg equilibrium. The allele and genotype distributions of the polymorphisms tested were similar among cases and controls, such that the relative risk of future stroke was 0.87 for CD14 C(-260)T (95% CI=0.69 to 1.11; P=0.27) and 0.99 for CD18 codon 441 (95% CI=0.77 to 1.28; P=0.96) assuming an additive mode of inheritance. No evidence of association was observed assuming dominant or recessive model, and similar null results were observed in subgroup analysis restricted to thromboembolic events CONCLUSIONS: In this large, prospective study, we found little evidence that the two previously described polymorphisms in the CD14 and CD18 genes are associated with risks of future stroke.
Authors: John W Cole; David W Brown; Wayne H Giles; Oscar C Stine; Jeffrey R O'Connell; Braxton D Mitchell; John D Sorkin; Marcella A Wozniak; Barney J Stern; Mary J Sparks; Mark T Dobbins; Latasha T Shoffner; Nancy K Zappala; Laurie J Reinhart; Steven J Kittner Journal: Thromb J Date: 2008-08-26