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dc.contributor.authorBlasko, Bernadett*
dc.contributor.authorKolka, Ragnhildur*
dc.contributor.authorThorbjornsdottir, Perla*
dc.contributor.authorSigurdarson, Sigurdur Thor*
dc.contributor.authorSigurdsson, Gardar*
dc.contributor.authorRónai, Zsolt*
dc.contributor.authorSasvári-Székely, Mária*
dc.contributor.authorBödvarsson, Sigurdur*
dc.contributor.authorThorgeirsson, Gudmundur*
dc.contributor.authorProhászka, Zoltán*
dc.contributor.authorKovács, Margit*
dc.contributor.authorFüst, George*
dc.contributor.authorArason, Gudmundur Johann*
dc.date.accessioned2009-08-05T11:23:05Z
dc.date.available2009-08-05T11:23:05Z
dc.date.issued2008-01-01
dc.date.submitted2009-08-05
dc.identifier.citationInt. Immunol. 2008, 20(1):31-7en
dc.identifier.issn1460-2377
dc.identifier.pmid18032375
dc.identifier.doi10.1093/intimm/dxm117
dc.identifier.urihttp://hdl.handle.net/2336/76327
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractBACKGROUND 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.
dc.language.isoenen
dc.publisherOxford University Press,en
dc.relation.urlhttp://dx.doi.org/10.1093/intimm/dxm117en
dc.subject.meshAgeden
dc.subject.meshAged, 80 and overen
dc.subject.meshComplement C4ben
dc.subject.meshFemaleen
dc.subject.meshGene Dosageen
dc.subject.meshGenetic Predisposition to Diseaseen
dc.subject.meshHumansen
dc.subject.meshIcelanden
dc.subject.meshLymphotoxin-alphaen
dc.subject.meshMaleen
dc.subject.meshMyocardial Infarctionen
dc.subject.meshPolymerase Chain Reactionen
dc.subject.meshPolymorphism, Single Nucleotideen
dc.subject.meshRisk Factorsen
dc.subject.meshSmokingen
dc.subject.meshSurvival Analysisen
dc.titleLow complement C4B gene copy number predicts short-term mortality after acute myocardial infarction.en
dc.typeArticleen
dc.contributor.departmentResearch Group of Inflammation Biology and Immunogenomics, Semmelweis University and Hungarian Academy of Sciences, Budapest, Hungary.en
dc.identifier.journalInternational immunologyen
html.description.abstractBACKGROUND 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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