title: Genetic approaches in the understanding of Toxic Oil Syndrome.
abstract: 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.
authors.affiliation: Immunology Department, Fundación Jiménez Díaz-IDC-Capio, Clínica de la Concepción, Av. Reyes Católicos 2, 28040 Madrid, Spain. bcardaba@fjd.es
authors.forename: Blanca
authors.initials: B
authors.lastname: Cárdaba
authors.forename: Victoria
authors.initials: V
authors.lastname: del Pozo
authors.forename: Soledad
authors.initials: S
authors.lastname: Gallardo
authors.forename: Pilar
authors.initials: P
authors.lastname: Palomino
authors.forename: Manuel
authors.initials: M
authors.lastname: Posada
authors.forename: Carlos
authors.initials: C
authors.lastname: Lahoz
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D004802:Eosinophilia / Q000209:etiology; D005229:Fatty Acids, Monounsaturated; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008107:Liver Diseases / Q000209:etiology; D016015:Logistic Models; D008171:Lung Diseases / Q000209:etiology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D016017:Odds Ratio; D010938:Plant Oils / Q000008:administration & dosage / Q000506:poisoning*; D000074262:Rapeseed Oil; D012595:Scleroderma, Systemic / Q000209:etiology; D012737:Sex Factors; D013030:Spain; D013577:Syndrome
chemical_list: D005229:Fatty Acids, Monounsaturated; D005819:Genetic Markers; D010938:Plant Oils; D000074262:Rapeseed Oil