Low complement C4B gene copy number predicts short-term mortality after acute myocardial infarction.
OBJECTIVE
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.
Blaskó
Bernadett
B
Research Group of Inflammation Biology and Immunogenomics, Semmelweis University and Hungarian Academy of Sciences, Budapest, Hungary.
Kolka
Ragnhildur
R
Thorbjornsdottir
Perla
P
Sigurdarson
Sigurdur Thór
ST
Sigurdsson
Gardar
G
Rónai
Zsolt
Z
Sasvári-Székely
Mária
M
Bödvarsson
Sigurdur
S
Thorgeirsson
Gudmundur
G
Prohászka
Zoltán
Z
Kovács
Margit
M
Füst
George
G
Arason
Gudmundur Jóhann
GJ
D000368:Aged; D000369:Aged, 80 and over; D015935:Complement C4b / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D006801:Humans; D007055:Iceland; D008233:Lymphotoxin-alpha / Q000235:genetics; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics* / Q000401:mortality*; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D016019:Survival Analysis
D008233:Lymphotoxin-alpha; D015935:Complement C4b