It is found on chromosome 11 in humans in a locus with other inflammatory caspases.[5]CASP12orthologs[6] have been identified in numerous mammals for which complete genome data are available.
Clinical significance
The CASP12 gene is subject to polymorphism, which can generate a full-length caspase protein (Csp12L) or an inactive truncated form (Csp12S). The functional form appears to be confined to people of African descent and is linked with susceptibility to sepsis; people carrying the functional gene have decreased responses to bacterial molecules such as lipopolysaccharide (LPS).[7][8]
A study in May 2009 by McGill University Health Centre has suggested that estrogen may serve to block the production of caspase-12, resulting in a stronger inflammatory reaction to bacterial pathogens. The trials were carried out on laboratory mice which had been implanted with the human caspase-12 gene.[9][10][11]
The inactive truncated form (Csp12S) of the CASP12 gene was spread and nearly fixed in non-African populations due to positive selection beginning perhaps 60–100 thousand years ago. Its selective advantage is thought to be sepsis resistance in populations that experienced more infectious diseases as population sizes and densities increased.[12][13]
^Saleh, Maya Mathison; John C. Wolinski; Melissa K. Bensinger; Steve J. Fitzgerald; Patrick Droin; Nathalie Ulevitch; Richard J. Green; Douglas R. Nicholson; Donald W. (2006). "Enhanced bacterial clearance and sepsis resistance in caspase-12-deficient mice". Nature. 440 (7087): 1064–1068. Bibcode:2006Natur.440.1064S. doi:10.1038/nature04656. PMID16625199. S2CID4321520.
