Genetic approaches in the understanding of Toxic Oil Syndrome

The Toxic Oil Syndrome (TOS) is a multisystemic disease that occurred in Spain in 1981 due to the ingestion of rapeseed oil denatured with 2% aniline. Female prevalence and the different clinical evolution even inside the same family (similar exposition), pointed to genetic implications. Furthermore, HLA-DR2 was increased in patients dead because of TOS. Th2 activation and eosinophilia implicated immunological mechanisms. For those reasons we firstly decided, to do a genome-wide search by linkage mapping set along the chromosome 6 (where HLA loci are located), to identify loci associated to the TOS development. The design was case-control-matched (n = 328). By this procedure, microsatellite (near to HLA) was related with the patients. After fine-mapping around this marker, we defined four more closely related to TOS-, , and . Secondly, we analysed in 420 patients, the association of these four markers with 14 TOS clinical phenotypes. We demonstrated that alveolar infiltration, liver disease and scleroderma are clearly associated with . As conclusion, we have identified in chromosome 6, a region where are located some genes related with autoimmune diseases, associated with certain TOS phenotypes, pointing out the possible role of autoimmune reactions in the pathogenesis of the disease.