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.
Cárdaba
Blanca
B
Immunology Department, Fundación Jiménez Díaz-IDC-Capio, Clínica de la Concepción, Av. Reyes Católicos 2, 28040 Madrid, Spain. bcardaba@fjd.es
del Pozo
Victoria
V
Gallardo
Soledad
S
Palomino
Pilar
P
Posada
Manuel
M
Lahoz
Carlos
C
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
D005229:Fatty Acids, Monounsaturated; D005819:Genetic Markers; D010938:Plant Oils; D000074262:Rapeseed Oil