Usefulness of combining complement factor H and C-reactive protein genetic profiles for predicting myocardial infarction (from the Rotterdam Study).
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.
Kardys
Isabella
I
Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands.
de Maat
Moniek P M
MP
Klaver
Caroline C W
CC
Despriet
Dominiek D G
DD
Uitterlinden
André G
AG
Hofman
Albert
A
de Jong
Paulus T V M
PT
Witteman
Jacqueline C M
JC
D000368:Aged; D000483:Alleles; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism; D017242:Complement Factor H / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D009426:Netherlands / Q000453:epidemiology; D011110:Polymorphism, Genetic; D011159:Population Surveillance; D015995:Prevalence; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors
D015415:Biomarkers; D017242:Complement Factor H; D002097:C-Reactive Protein