Presence of the functional Caspase-12 allele in Indian subpopulations (93.25)

Abstract

Abstract In rodents, caspase-12 (casp12) is a negative regulator of interleukin-1 production. Most humans lack a functional CASP12 gene, with a non-functional variant (CASP12p1), found in 100% of the Caucasian and East Asian population, and in approximately 80% of people of African descent. However, 20% of sub-Saharan Africans carry an intact allele of CASP12, which produces a full-length non-catalytic proenzyme and is associated with an increased risk of sepsis. Using PCR-based single nucleotide polymorphism analysis and DNA sequencing, we examined CASP12 allele distribution in individuals from Central and Southern Asia and found that CASP12 was significantly present in members of the Dravidian language group (the predominant ethnic and language group of southern India), particularly persons from Tamil Nadu. The CASP12 allele also occurs at a higher frequency in individuals with the Australoid morphotype that predominates in southern India, as compared to those with the Caucasoid morphotype prevalent in central and northern India. The data suggest that there is a north-to-south gradient of increasing prevalence for the CASP12 allele. As the CASP12p1 allele has been rigorously selected for in populations outside of Africa and southern Asia, we hypothesize that a pathogen that exploits the inflammatory immune response in Africa and southern India may be exerting positive selective pressure on CASP12.