CLINICAL RESEARCH: ACUTE MYOCARDIAL INFARCTION
A Common Polymorphism in the Complement Factor H Gene Is Associated With Increased Risk of Myocardial Infarction
The Rotterdam Study
Isabella Kardys, MD*,
Caroline C.W. Klaver, MD, PhD*, ,
Dominiek D.G. Despriet, MD*,,
Arthur A.B. Bergen, PhD¶,||,
André G. Uitterlinden, PhD ,
Albert Hofman, MD, PhD*,
Ben A. Oostra, PhD ,
Cornelia M. Van Duijn, PhD*,
Paulus T.V.M. de Jong, MD, PhD*,¶,# and
Jacqueline C.M. Witteman, PhD*,*
* Department of Epidemiology & Biostatistics, Erasmus Medical Center, Rotterdam, the Netherlands
Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands
¶ Department of Ophthalmogenetics, Netherlands Ophthalmic Research Institute, Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands
|| Department of Clinical Genetics, Academic Medical Center, Amsterdam, the Netherlands
# Department of Ophthalmology, Academic Medical Center, Amsterdam, the Netherlands
Manuscript received September 15, 2005;
revised manuscript received November 17, 2005,
accepted November 28, 2005.
* Reprint requests and correspondence: Dr. Jacqueline C. M. Witteman, Erasmus Medical Center, Department of Epidemiology & Biostatistics, P.O. Box 1738, 3000 DR Rotterdam, the Netherlands (Email: j.witteman{at}erasmusmc.nl).
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.
|
Abbreviations and Acronyms
| | CABG = coronary artery bypass grafting | | CFH = complement inhibitor factor H | | CI = confidence interval | | CRP = C-reactive protein | | GP = general practitioner | | HDL = high-density lipoprotein | | PTCA = percutaneous transluminal coronary angioplasty |
|
This article has been cited by other articles:
|
|
|
|
 
K. C.M.C. Koeijvoets, S. P. Mooijaart, G. M. Dallinga-Thie, J. C. Defesche, E. W. Steyerberg, R. G.J. Westendorp, J. J.P. Kastelein, P. M. van Hagen, and E. J.G. Sijbrands
Complement factor H Y402H decreases cardiovascular disease risk in patients with familial hypercholesterolaemia
Eur. Heart J.,
March 1, 2009;
30(5):
618 - 623.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Ormsby, S. Ranganathan, J. C. Tong, K. M. Griggs, D. P. Dimasi, A. W. Hewitt, K. P. Burdon, J. E. Craig, J. Hoh, and D. L. Gordon
Functional and Structural Implications of the Complement Factor H Y402H Polymorphism Associated with Age-Related Macular Degeneration
Invest. Ophthalmol. Vis. Sci.,
May 1, 2008;
49(5):
1763 - 1770.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. B. Damani and E. J. Topol
Future Use of Genomics in Coronary Artery Disease
J. Am. Coll. Cardiol.,
November 13, 2007;
50(20):
1933 - 1940.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. E. K. Wolf-Schnurrbusch, N. Roosli, E. Weyermann, M. R. Heldner, K. Hohne, and S. Wolf
Ethnic Differences in Macular Pigment Density and Distribution
Invest. Ophthalmol. Vis. Sci.,
August 1, 2007;
48(8):
3783 - 3787.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. J. de Jong, M. K. Ikram, D. D. G. Despriet, A. G. Uitterlinden, A. Hofman, M. M. B. Breteler, and P. T. V. M. de Jong
Complement Factor H Polymorphism, Inflammatory Mediators, and Retinal Vessel Diameters: The Rotterdam Study
Invest. Ophthalmol. Vis. Sci.,
July 1, 2007;
48(7):
3014 - 3018.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. K. Pai, J. E. Manson, K. M. Rexrode, C. M. Albert, D. J. Hunter, and E. B. Rimm
Complement factor H (Y402H) polymorphism and risk of coronary heart disease in US men and women
Eur. Heart J.,
June 1, 2007;
28(11):
1297 - 1303.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Pulido, J. P. McConnell, L. M. Peterson, W. E. Highsmith, R. J. Lennon, S. C. Bryant, P. B. Berger, and V. Somers
Relationship Between Age-Related Macular Degeneration-Associated Variants of Complement Factor H and LOC387715 With Coronary Artery Disease
Mayo Clin. Proc.,
March 1, 2007;
82(3):
301 - 307.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. J. Topol, J. Smith, E. F. Plow, and Q. K. Wang
Genetic susceptibility to myocardial infarction and coronary artery disease
Hum. Mol. Genet.,
October 15, 2006;
15(suppl_2):
R117 - R123.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Clark, V. A. Higman, B. Mulloy, S. J. Perkins, S. M. Lea, R. B. Sim, and A. J. Day
His-384 Allotypic Variant of Factor H Associated with Age-related Macular Degeneration Has Different Heparin Binding Properties from the Non-disease-associated Form
J. Biol. Chem.,
August 25, 2006;
281(34):
24713 - 24720.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
