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

Atherosclerosis. 2006 Aug;187(2):332-5. doi: 10.1016/j.atherosclerosis.2005.09.009. Epub 2005 Oct 17.

Abstract

Objectives: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aspirin / therapeutic use
  • Brain Ischemia / epidemiology
  • Brain Ischemia / genetics
  • Brain Ischemia / prevention & control
  • C-Reactive Protein / metabolism*
  • Cardiovascular Diseases / epidemiology*
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / prevention & control
  • Case-Control Studies
  • Complement Factor H / genetics*
  • European Continental Ancestry Group / genetics
  • European Continental Ancestry Group / statistics & numerical data
  • Gene Frequency
  • Genetic Predisposition to Disease / epidemiology
  • Genotype
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / genetics
  • Myocardial Infarction / prevention & control
  • Platelet Aggregation Inhibitors / therapeutic use
  • Polymorphism, Genetic*
  • Prospective Studies
  • Risk Factors
  • Stroke / epidemiology
  • Stroke / genetics
  • Stroke / prevention & control
  • Venous Thrombosis / epidemiology
  • Venous Thrombosis / genetics
  • Venous Thrombosis / prevention & control
  • Vitamins / therapeutic use
  • beta Carotene / therapeutic use

Substances

  • Platelet Aggregation Inhibitors
  • Vitamins
  • beta Carotene
  • Complement Factor H
  • C-Reactive Protein
  • Aspirin