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A prospective evaluation of the CD14 and CD18 gene polymorphisms and risk of stroke
Robert Y L Zee1, David Bates, Paul M Ridker
1Center 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
Insights
Genetic variations in CD14 and CD18 genes do not appear to increase stroke risk. This large prospective study found no significant association between these polymorphisms and the incidence of stroke.
Area of Science:
- Genetics
- Cardiovascular Disease Epidemiology
- Molecular Biology
Background:
- Genetic polymorphisms in CD14 and CD18 genes have been suggested as potential risk factors for atherothrombosis.
- Prospective data linking these specific gene polymorphisms to subsequent stroke risk were previously lacking.
Purpose of the Study:
- To investigate the association between CD14 C(-260)T and CD18 codon 441 gene polymorphisms and the incidence of stroke.
- To evaluate these genetic variations as potential risk factors for atherothrombosis and stroke in a large prospective cohort.
Main Methods:
- A nested case-control study design was employed within the Physicians' Health Study, following 14,916 men over 12 years.
- 338 stroke cases were matched with 338 controls who remained disease-free, with polymorphisms analyzed using polymerase chain reaction and gel electrophoresis.
Main Results:
- No significant differences in allele or genotype distributions were found between stroke cases and controls for both CD14 and CD18 polymorphisms.
- The relative risk for stroke was 0.87 for CD14 C(-260)T and 0.99 for CD18 codon 441, with no evidence of association under additive, dominant, or recessive models.
Conclusions:
- This large prospective study found minimal evidence to support an association between the investigated CD14 and CD18 gene polymorphisms and the risk of future stroke.
- The findings suggest that these specific genetic variations may not be significant risk factors for stroke incidence.
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.