A common polymorphism in the complement factor H gene is associated with increased risk of myocardial infarction: the Rotterdam Study.
OBJECTIVE
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.
Kardys
Isabella
I
Department of Epidemiology & Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands.
Klaver
Caroline C W
CC
Despriet
Dominiek D G
DD
Bergen
Arthur A B
AA
Uitterlinden
André G
AG
Hofman
Albert
A
Oostra
Ben A
BA
Van Duijn
Cornelia M
CM
de Jong
Paulus T V M
PT
Witteman
Jacqueline C M
JC
D000368:Aged; D002784:Cholesterol / Q000097:blood; D017242:Complement Factor H / Q000235:genetics*; D048909:Diabetes Complications; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006639:Histidine; D006720:Homozygote; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D014443:Tyrosine
D014443:Tyrosine; D006639:Histidine; D017242:Complement Factor H; D002784:Cholesterol