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Toxic oil syndrome (TOS) was an epidemic which broke out in Spain in 1981, caused by the ingestion of rapeseed oil denatured with 2percent aniline and sold illegally as edible oil. More than 20,000 people were affected and mortality rate was 8.4percent. Genetic susceptibility appears to be involved in the pathology of this disease. Several reports have described association between the chronic stage of the disease and DR-DQ antigens (DR3, DR4, DR2 and DQ8). In the present work, we have reassessed the HLA class II antigens in a well-designed case-control study. Triplets of subjects (nequals265) composed by chronic patients (nequals117), non-affected family members (nequals71) and non-related controls (nequals77) were studied. Also, HLA class II antigens were analyzed in patients who had died from TOS (nequals34) and in TOS control patients who died from other non-TOS related causes (nequals13). Regarding surviving patients no significant association was found between HLA and disease. In contrast, an increase in phenotypic frequency of DR2 antigen, was found in patients who had died from TOS (73.5percent) compared with the whole study group: TOS-affected alive patients (25.6percent, corrected P<0.001), non-affected family members (28.5percent, corrected P<0.001), non-related controls (23.9percent, corrected P<0.001) and dead controls (38.4percent, Pequals0.03). [ABSTRACT FROM AUTHOR]