title: Low complement C4B gene copy number predicts short-term mortality after acute myocardial infarction.
abstract: 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.
authors.affiliation: Research Group of Inflammation Biology and Immunogenomics, Semmelweis University and Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Bernadett
authors.initials: B
authors.lastname: Blaskó
authors.forename: Ragnhildur
authors.initials: R
authors.lastname: Kolka
authors.forename: Perla
authors.initials: P
authors.lastname: Thorbjornsdottir
authors.forename: Sigurdur Thór
authors.initials: ST
authors.lastname: Sigurdarson
authors.forename: Gardar
authors.initials: G
authors.lastname: Sigurdsson
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Rónai
authors.forename: Mária
authors.initials: M
authors.lastname: Sasvári-Székely
authors.forename: Sigurdur
authors.initials: S
authors.lastname: Bödvarsson
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Thorgeirsson
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Prohászka
authors.forename: Margit
authors.initials: M
authors.lastname: Kovács
authors.forename: George
authors.initials: G
authors.lastname: Füst
authors.forename: Gudmundur Jóhann
authors.initials: GJ
authors.lastname: Arason
mesh_terms: 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
chemical_list: D008233:Lymphotoxin-alpha; D015935:Complement C4b