Abstract 3908: Interaction between C-Reactive Protein and Complement Inhibitor Factor H and Risk of Myocardial Infarction. The Rotterdam Study.
The Rsch Institute for Diseases in the Elderly(RIDE) supported this study (grant 948 – 00 – 016)
Background Complement inhibitor factor H (CFH) is an important regulator of the alternative complement cascade. Binding of C-reactive protein (CRP) to CFH augments the ability of CFH to down-regulate the effect of complement in atherosclerotic lesions. The CFH Tyr402His polymorphism (rs1061170) has been suggested to influence the ability of CFH to bind CRP. We hypothesized, that the combined presence of unfavorable genetic CRP and CFH profiles predicts myocardial infarction.
Methods and results The Rotterdam Study is a population-based cohort study among 7983 men and women aged ≥55 years. Participants with history of coronary heart disease were excluded. The CFH Tyr402His polymorphism was determined (His allele frequency 36%). Using three tagging polymorphisms (rs1130864, rs1205, rs3093068), CRP haplotypes were inferred (1=CTC, 2=TCC, 3=CCC; frequencies 32.8, 31.7 and 29.5% respectively). Subsequently, participants were grouped according to both CFH genotype (TyrTyr [reference], TyrHis, HisHis) and CRP haplotype (haplotype 1 homozygotes [reference], haplotype 2 carriers, haplotype 3 carriers). CRP gene haplotypes 2 and 3 were associated with higher CRP serum levels, but were not significantly associated with myocardial infarction. CFH HisHis genotype was associated with myocardial infarction (multivariable adjusted hazard ratio 1.8, 95% CI 1.2–2.6). CFH His homozygotes that were also CRP haplotype 3 carriers had an age-and sex-adjusted hazard ratio of 7.8 (95% CI 1.8–33.0) to develop myocardial infarction.
Conclusions This population-based study suggests that the combined presence of unfavorable genetic CRP and CFH profiles predicts myocardial infarction.