@article {309735,
	title = {Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms.},
	journal = {Nature},
	volume = {429},
	year = {2004},
	month = {2004 May 6},
	pages = {75-9},
	abstract = {<p>Caspases mediate essential key proteolytic events in inflammatory cascades and the apoptotic cell death pathway. Human caspases functionally segregate into two distinct subfamilies: those involved in cytokine maturation (caspase-1, -4 and -5) and those involved in cellular apoptosis (caspase-2, -3, -6, -7, -8, -9 and -10). Although caspase-12 is phylogenetically related to the cytokine maturation caspases, in mice it has been proposed as a mediator of apoptosis induced by endoplasmic reticulum stress including amyloid-beta cytotoxicity, suggesting that it might contribute to the pathogenesis of Alzheimer{\textquoteright}s disease. Here we show that a single nucleotide polymorphism in caspase-12 in humans results in the synthesis of either a truncated protein (Csp12-S) or a full-length caspase proenzyme (Csp12-L). The read-through single nucleotide polymorphism encoding Csp12-L is confined to populations of African descent and confers hypo-responsiveness to lipopolysaccharide-stimulated cytokine production in ex vivo whole blood, but has no significant effect on apoptotic sensitivity. In a preliminary study, we find that the frequency of the Csp12-L allele is increased in African American individuals with severe sepsis. Thus, Csp12-L attenuates the inflammatory and innate immune response to endotoxins and in doing so may constitute a risk factor for developing sepsis.</p>
},
	keywords = {Africa, African Americans, Alzheimer Disease, Animals, Apoptosis, Base Sequence, Case-Control Studies, Caspase 12, Caspases, Concanavalin A, Cytokines, Endoplasmic Reticulum, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Inflammation, Lipopolysaccharides, NF-kappa B, Polymorphism, Single Nucleotide, Primates, Sepsis},
	issn = {1476-4687},
	doi = {10.1038/nature02451},
	author = {Saleh, Maya and Vaillancourt, John P and Graham, Rona K and Huyck, Matthew and Srinivasula, Srinivasa M and Alnemri, Emad S and Steinberg, Martin H and Nolan, Vikki and Baldwin, Clinton T and Hotchkiss, Richard S and Buchman, Timothy G and Zehnbauer, Barbara A and Hayden, Michael R and Farrer, Lindsay A and Roy, Sophie and Nicholson, Donald W}
}
