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Low complement C4B gene copy number predicts short-term mortality after acute myocardial infarction
Bernadett Blaskó1, Ragnhildur Kolka, Perla Thorbjornsdottir
1Research Group of Inflammation Biology and Immunogenomics, Semmelweis University and Hungarian Academy of Sciences, Budapest, Hungary.
Insights
Low C4B gene copy number is a significant risk factor for 1-year mortality after acute myocardial infarction, particularly in smoking Icelandic patients. The LTA 252 G allele did not show this association in the studied Caucasian population.
Area of Science:
- Genetics
- Cardiovascular Medicine
- Immunogenetics
Background:
- Genetic factors influence risk of death after acute coronary syndrome.
- Low C4B gene copy number (C4B*Q0 genotype) is linked to cardiovascular disease morbidity and mortality.
- The LTA +252 G allele has been associated with CVD mortality in Oriental populations.
Purpose of the Study:
- To investigate the association between complement component C4 gene copy number (C4A and C4B) and lymphotoxin-alpha (LTA) gene polymorphism with mortality after acute myocardial infarction (AMI).
Main Methods:
- Studied 142 Icelandic patients post-AMI.
- Quantified C4A and C4B gene copy numbers using real-time PCR.
- Assessed LTA +252 A>G single-nucleotide polymorphism (SNP) via PCR-RFLP.
Main Results:
- The C4B*Q0 genotype was strongly associated with 1-year mortality (HR 3.50, P=0.008), specifically in patients who had ever smoked.
- C4A gene copy number did not correlate with increased mortality risk.
- LTA +252 SNP did not confer an increased risk of mortality after AMI.
Conclusions:
- Low C4B gene copy number is a significant risk factor for short-term mortality post-AMI in smoking Icelandic patients.
- The LTA +252 G allele is not identified as a risk factor for AMI mortality in this Caucasian cohort.
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.
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