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

Bernadett Blaskó, Ragnhildur Kolka, Perla Thorbjornsdottir, Sigurdur Thór Sigurdarson, Gardar Sigurdsson, Zsolt Rónai, Mária Sasvári-székely, Sigurdur Bodie;dvarsson, Gudmundur Thorgeirsson, Zoltán Prohászka, Margit Kovács, George Füst, Gudmundur Jóhann Arason

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)31-37
Number of pages7
JournalInternational Immunology
Volume20
Issue number1
DOIs
StatePublished - Jan 2008

Keywords

  • Acute myocardial infarction
  • C4
  • C4B
  • Copy number polymorphism
  • Mortality

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    Blaskó, B., Kolka, R., Thorbjornsdottir, P., Sigurdarson, S. T., Sigurdsson, G., Rónai, Z., Sasvári-székely, M., Bodie;dvarsson, S., Thorgeirsson, G., Prohászka, Z., Kovács, M., Füst, G., & Arason, G. J. (2008). Low complement C4B gene copy number predicts short-term mortality after acute myocardial infarction. International Immunology, 20(1), 31-37. https://doi.org/10.1093/intimm/dxm117