Usefulness of combining complement factor H and C-reactive protein genetic profiles for predicting myocardial
Isabella Kardys1, Moniek P M de Maat, Caroline C W Klaver
1Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands.
Insights
Certain genetic profiles for complement factor H (CFH) and C-reactive protein (CRP) increase myocardial infarction (MI) risk. Individuals with specific CFH and CRP gene variants face a significantly higher risk of developing MI.
Area of Science:
- Genetics
- Cardiovascular Medicine
- Immunology
Background:
- Complement factor H (CFH) regulates the complement cascade.
- C-reactive protein (CRP) binding to CFH modulates complement activity in atherosclerosis.
- The CFH Tyr402His polymorphism may affect CFH's CRP binding capability.
Purpose of the Study:
- To investigate the association between combined genetic profiles of CFH and CRP and the risk of myocardial infarction (MI).
Main Methods:
- The Rotterdam Study cohort included 7,983 individuals aged 55+.
- CFH Tyr402His polymorphism and CRP haplotypes (using tagging SNPs) were determined.
- Participants were genotyped for CFH and categorized by CRP haplotype.
Main Results:
- A significantly elevated risk of MI was observed in individuals with the CFH His(402) homozygote genotype and CRP haplotype 3.
- This combined genetic profile showed an adjusted hazard ratio of 5.9 for MI development compared to the reference group.
Conclusions:
- The study suggests that specific combinations of unfavorable CFH and CRP genetic profiles are associated with an increased risk of myocardial infarction.
- These findings highlight the potential role of combined genetic risk factors in cardiovascular disease etiology.
Abstract:
Complement factor H (CFH) is an important regulator of the complement cascade. Binding of C-reactive protein (CRP) to CFH augments the ability of CFH to downregulate the effect of complement in atherosclerotic lesions. The CFH Tyr402His polymorphism has been suggested to influence the ability of CFH to bind CRP. We hypothesized that the combined presence of unfavorable CRP and CFH genetic profiles is associated with risk of myocardial infarction (MI). The Rotterdam Study is a population-based cohort study in 7,983 men and women aged > or =55 years. The CFH Tyr402His (rs1061170) polymorphism was determined (His(402) allele 37%), and using 3 tagging polymorphisms (rs1130864, rs1205, and rs3093068), CRP haplotypes were inferred (1 = CTC, 2 = TCC, 3 = CCC, 4 = CCG; frequencies of 33%, 32%, 30%, and 6%, respectively). Participants were grouped by CFH genotype (TyrTyr [reference], TyrHis, and HisHis) and CRP haplotype (haplotype 1 homozygotes [reference], haplotype 2 carriers, haplotype 3 carriers, and haplotype 4 carriers), which resulted in a total of 12 groups. CFH His(402) homozygotes who were also CRP haplotype 3 carriers had an age- and gender-adjusted hazard ratio of 5.9 (95% confidence interval 2.1 to 16.5) to develop MI compared with the reference group. In conclusion, this population-based study suggests that the combined presence of unfavorable CFH and CRP genetic profiles is associated with risk of MI.
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