OCTN genes: Susceptibility genes for autoimmune diseases?

Genetic studies in polygenic autoimmune diseases (Rheumatoid arthritis, inflammatory bowel disease, etc) have moved from identifying by linkage studies those genomic regions involved in susceptibility, to the precise ascertainment of specific variants molecularly related to the disease by association studies. One of the regions which attracted more attention is 5q31, linked to inflammatory bowel and allergic diseases because it harbours the cytokine-cluster comprising IL4, IL5 and IL13, among others. A surprising result of subsequent association studies, both in Crohn's disease and in rheumatoid arthritis, was that the susceptibility genes in that region turned out to be, not any of the cytokine genes, but two organic cation transporters, OCTN1 and OCTN2 coded by the SLC22A4 and SLC22A5 genes respectively, not previously anticipated as relevant for the immune response. During the last two years there has been a lively debate in the immunogenetic literature on whether these genes are truly responsible of the increased susceptibility to the disease, or they are simply passively carried on chromosome 5q31 by linkage disequilibrium with an as-yet-unknown etiologic variant. In the present review, we aim at offering a brief glance of the current status in this field.