Linked Life Data

16778130

Source:http://linkedlifedata.com/resource/pubmed/id/16778130

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pubmed-article:16778130pubmed:abstractTextCaspase-1 processes the interleukin (IL)-1beta and IL-18 inactive precursors to the biologically active cytokines that are known to have proatherogenic effects. The present study investigated the genetic variability of the CASP1 gene and plasma levels of caspase-1 in relation to cardiovascular risk. In Europeans, 3 tag SNPs captured 4 common haplotypes of the CASP1 gene. Among these, the A(in6) allele of the G+7/in6A polymorphism was less frequent in 246 cases with myocardial infarction and a parental history of disease than in 253 controls free of familial history of disease (0.13+/-0.02 versus 0.20+/-0.02; P=0.005). However, in a larger case/control study (n=1774), these effects are borderline restricted to the UK population. In a prospective cohort of 1168 patients with coronary artery disease followed up during a median period of 6.0 years, the A(in6) allele exhibited a borderline association with future cardiovascular death (hazard ratio [HR]: 0.64, 0.41 to 1.01; P=0.053) and was associated with lower serum IL-18 levels (P=0.014). Baseline caspase-1 levels in the top quartile of the distribution were predictive of cardiovascular deaths (HR=3.62, 1.81 to 7.27; P=0.0003 compared with the bottom quartile). Finally, in vitro assays of allelic imbalance showed that the CASP1 haplotype carrying the A(in6) allele was associated with a lower mRNA expression. These results indicate that caspase-1 levels are predictive of future cardiovascular death in patients with coronary artery disease. The role of CASP1 genetic variations in the susceptibility to myocardial infarction requires further investigation.lld:pubmed
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pubmed-article:16778130pubmed:articleTitleHaplotypes of the caspase-1 gene, plasma caspase-1 levels, and cardiovascular risk.lld:pubmed
pubmed-article:16778130pubmed:affiliationDepartment of Medicine II, Johannes Gutenberg-University Mainz, Mainz, Germany. blankenberg@2-med.klinik.uni-mainz.delld:pubmed
pubmed-article:16778130pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:16778130pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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