Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

OBJECTIVES: This study was designed to investigate the association between a common polymorphism (Tyr402His, rs1061170) in the complement factor H (CFH) gene and risk of coronary heart disease. BACKGROUND: The evidence that inflammation is an important mechanism in atherogenesis is growing. C-reactive protein (CRP), complement factors, and complement regulatory factors have all been linked to coronary heart disease. The CFH gene is an important regulator of the alternative complement cascade. We investigated its association with coronary heart disease. METHODS: The study was embedded in the Rotterdam Study, a prospective population-based study among men and women aged 55 years and over. A total of 5,520 participants without history of coronary heart disease was genotyped for the Tyr402His polymorphism of the CFH gene. Cox proportional hazards analysis was used to determine risk of myocardial infarction for Tyr402His genotypes. RESULTS: Mean age among participants was 69.5 years (SD 9.1 years). The overall frequency of the His allele was 36%; genotype frequencies were 41%, 45%, and 14% for TyrTyr, TyrHis, and HisHis, respectively. During a mean follow-up period of 8.4 years, 226 myocardial infarctions occurred. After adjustment for age, gender, established cardiovascular risk factors, and CRP level, HisHis homozygotes had a hazard ratio of 1.77 (95% confidence interval 1.23 to 2.55) for myocardial infarction. Total cholesterol level, diabetes mellitus, and smoking modified the effect. The Tyr402His polymorphism was not associated with established cardiovascular risk factors or CRP level. CONCLUSIONS: Our data suggest that the CFH gene determines susceptibility to myocardial infarction. This finding underscores the importance of the alternative complement system in cardiovascular disease.

Original publication

DOI

10.1016/j.jacc.2005.11.076

Type

Journal article

Journal

Journal of the American College of Cardiology

Publication Date

04/2006

Volume

47

Pages

1568 - 1575

Addresses

Department of Epidemiology & Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands.

Keywords

Humans, Myocardial Infarction, Diabetes Complications, Genetic Predisposition to Disease, Cholesterol, Tyrosine, Histidine, Complement Factor H, Incidence, Proportional Hazards Models, Risk Factors, Smoking, Gene Frequency, Genotype, Homozygote, Polymorphism, Genetic, Aged, Middle Aged, Female, Male