Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Blankenberg, S. et al.

Blankenberg, Godefroy, Poirier, Rupprecht, Barbaux, Bickel, Nicaud, Schnabel, Kee, Morrison, Evans, Lackner, Cambien, Münzel, Tiret,

Haplotypes of the caspase-1 gene, plasma caspase-1 levels, and cardiovascular risk.

Caspase-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.[1]

References

Haplotypes of the caspase-1 gene, plasma caspase-1 levels, and cardiovascular risk. Blankenberg, S., Godefroy, T., Poirier, O., Rupprecht, H.J., Barbaux, S., Bickel, C., Nicaud, V., Schnabel, R., Kee, F., Morrison, C., Evans, A., Lackner, K.J., Cambien, F., Münzel, T., Tiret, L. Circ. Res. (2006) [Pubmed]

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