RESUMO
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.
Assuntos
Complemento C4b/genética , Dosagem de Genes , Predisposição Genética para Doença , Infarto do Miocárdio/genética , Infarto do Miocárdio/mortalidade , Fumar , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Islândia , Linfotoxina-alfa/genética , Masculino , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Fumar/efeitos adversos , Análise de SobrevidaRESUMO
We studied the distribution of complement C4, C3, and factor B allotypes in 423 healthy Icelandic subjects from 17 to 89 years of age. A marked decrease was observed in the carrier frequency of variant alleles of complement C4B (C4B(*)Q0) and C3 (C3(*)F). These results confirm our previous observations on Hungarian subjects and suggest a negative effect of C4B(*)Q0 on health or survival.
Assuntos
Envelhecimento/genética , Complemento C4b/genética , Proteínas do Sistema Complemento/genética , Variação Genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Complemento C3/genética , Frequência do Gene , Antígenos HLA-B/genética , Nível de Saúde , Humanos , Islândia , Pessoa de Meia-Idade , SobreviventesRESUMO
A strong association has been found between complement and common connective tissue diseases, such as systemic lupus erythema and Henoch Schoenlein Purpura. This has led to the notion that the pathogenesis of such diseases may involve a defect in the safe disposal of immune complexes, which is mediated by complement. To bring further light on this subject, a sensitive assay was developed to measure the ability of serum to prevent immune precipitation. This assay was then employed to study various Icelandic patient groups, and a defect in this function of complement was found to be common in patients with systemic lupus erythematosus and systemic sclerosis. Partial deficiency in complement C4A (C4A Q0) can not account for this defect, as it was not observed in patients with diabetes, gluten-sensitive enteropathy or autoimmune thyroiditis, in which C4A Q0 is common. The defect is strongly correlated with anti-C1q antibodies. Further studies are needed to test the possible role of anti-C1q antibodies in the pathogenesis of immune complex disease.