Complement factor H Y402H gene polymorphism, C-reactive protein, and risk of incident myocardial infarction, ischaemic stroke, and venous thromboembolism: a nested case-control study.
OBJECTIVE
An exonic polymorphism (Y402H) in the complement factor H (CFH) gene, which locates within the binding sites for heparin and C-reactive protein, has recently been described and hypothesized to play an important role in atherothrombosis.


METHODS
We, therefore, evaluated the CFH genetic variant Y402H amongst 685 Caucasian individuals who subsequently developed arterial or venous thrombotic event (incident myocardial infarction (MI), ischaemic stroke, or venous thromboembolism) and amongst 685 age- and smoking-matched Caucasian individuals who remained free of reported vascular disease during follow-up (controls) within the Physicians' Health Study cohort.


RESULTS
Genotype distribution for the polymorphism tested was in Hardy-Weinberg equilibrium in the control group. In contrast to expected results, we found no association of Y402H polymorphism with risk of atherothrombosis (adjusted: myocardial infarction, OR=1.09, 95%CI 0.88-1.36, p=0.43; ischaemic stroke, OR=1.11, 95%CI 0.81-1.54, p=0.52; venous thromboembolism, OR=1.41, 95%CI 0.88-2.24, p=0.15), nor with baseline plasma C-reactive protein levels [median (interquartile range) mg/L: YY, 1.39 (0.70-2.60); YH, 1.10 (0.57-2.16); HH, 1.00 (0.48-1.79); p=0.14].


CONCLUSIONS
In this large, prospective cohort of apparently healthy Caucasian men, we found no association of the complement factor H Y402H gene polymorphism with risk of incident thromboembolic events, nor with baseline levels of C-reactive protein.
Zee
Robert Y L
RY
Laboratory of Genetic Epidemiology, Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Avenue East, Boston, MA 02215, USA. rzee@rics.bwh.harvard.edu
Diehl
Kirsti A
KA
Ridker
Paul M
PM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000627:therapeutic use; D002545:Brain Ischemia / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control; D002097:C-Reactive Protein / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000235:genetics* / Q000517:prevention & control; D016022:Case-Control Studies; D017242:Complement Factor H / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control; D020246:Venous Thrombosis / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control; D014815:Vitamins / Q000627:therapeutic use; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data; D019207:beta Carotene / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D014815:Vitamins; D019207:beta Carotene; D017242:Complement Factor H; D002097:C-Reactive Protein; D001241:Aspirin