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International Immunology Advance Access published online on November 20, 2007
International Immunology, doi:10.1093/intimm/dxm117
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© The Japanese Society for Immunology. 2007. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Low complement C4B gene copy number predicts short-term mortality after acute myocardial infarction

Bernadett Blaskó1, Ragnhildur Kolka2, Perla Thorbjornsdottir2, Sigurður Thór Sigurðarson3, Garðar Sigurðsson3, Zsolt Rónai4, Mária Sasvári-Székely4, Sigurdur Böðvarsson3, Guðmundur Thorgeirsson3, Zoltán Prohászka1,5, Margit Kovács5, George Füst1,5 and Guðmundur Jóhann Arason2

1 Research Group of Inflammation Biology and Immunogenomics, Semmelweis University and Hungarian Academy of Sciences, Budapest, Hungary
2 Department of Immunology, Institute for Medical Laboratory Sciences
3 Department of Medicine, Landspítali University Hospital, Reykjavík, Iceland
4 Department of Medical Chemistry, Molecular Biology and Pathobiochemistry
5 Szentágothai János Knowledge Center and Third Department of Internal Medicine, Semmelweis University, Budapest, Hungary

Correspondence to: Correspondence to: G. Füst; E-mail: fustge{at}kut.sote.hu

Background and Objectives: Some recent data indicate that risk of death after acute coronary syndrome is under genetic control. Previously, we found that the C4B*Q0 genotype (low copy number of the C4B gene that encodes the fourth component of complement) is strongly associated with morbidity and mortality of cardiovascular diseases (CVD). The +252 G allele of the lymphotoxin-alpha (LTA) gene encoded close to the C4B gene was also reported to be related to CVD-related mortality in an Oriental population. Methods: The relationship between the copy number of the genes encoding the fourth component of complement (C4A and C4B) and LTA 252 single-nucleotide polymorphism (SNP) on the one hand and mortality after acute myocardial infarction (AMI) was studied in 142 Icelandic patients. The number of the C4A and C4B genes was determined in genomic DNA samples by a newly developed real-time PCR-based method; lymphotoxin-alpha (LTA) +252 A>G polymorphism was determined by PCR–restriction fragment length polymorphism analysis. Results: The C4B*Q0 genotype was found to be strongly associated with 1-year mortality, with a hazard ratio of 3.50 (1.38–8.87) (P = 0.008) (adjusted Cox regression analysis). This association was, however, restricted to ever-smoking patients. By contrast, neither C4A gene copy numbers nor LTA 252 SNP did confer increased risk of mortality after AMI. Conclusions: This observation indicates that low C4B copy number is a strong risk factor for short-term mortality after AMI in smoking Icelandic patients, whereas LTA 252 G allele is not a risk factor in Caucasian population.

Keywords: acute myocardial infarction, copy number polymorphism, C4, C4B, mortality

Transmitting editor: A. Falus

Received 21 May 2007, accepted 14 October 2007.


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