Rs12212067

rs12212067 is a noncoding SNP in the FOXO3A gene. This gene encodes the FOXO3 protein, a member of the forkhead box O family of transcription factors. These proteins are expressed in many cell types, with roles in cell-cycle control, metabolism, regulatory T cell development and apoptosis. It's role in cytokine production appears to be the key factor in this SNP's association with disease prognosis (but, interestingly, no role in disease susceptibility has been found to date).

rs12212067(G), the minor allele, is connected to the downregulation of TNF and several other proinflammatory cytokines in response to various antigens, and, the upregulation of IL10, a cytokine associated with anti-inflammatory effects. As elucidated in the cited study, this appears to explain the better outcomes for rs12212067(G) carriers of treatment for two auto-immune disorders, rheumatoid arthritis and Crohn's disease. As might be predicted for an infectious disease relying on an upregulated inflammatory response (which isn't happening as much with these carriers), this also leads to worse outcomes for carriers afflicted with malaria.;

More recently, a different group of researchers have reported that, at least in the patients they studied, rs12212067 is a far weaker predictor of the clinical outcome for Crohn's disease patients than is rs2066847, a SNP in the NOD2 gene.