2026-05-17T01:16:06Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/156162025-06-18T06:17:56Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19616
Repisalud
author
Ladona, Margarita G
author
Izquierdo Martinez, Maravillas
author
Posada De la Paz, Manuel
author
la Torre, Rafael de
author
Ampurdanés, Coral
author
Segura, Jordi
author
Sanz, Emilio J
funder
Instituto de Salud Carlos III
2023-03-13T15:16:04Z
2023-03-13T15:16:04Z
2001-04
Environ Health Perspect. 2001 Apr;109(4):369-75.
10.1289/ehp.01109369
0091-6765
Environmental health perspectives
11335185
http://hdl.handle.net/20.500.12105/15616
In 1981, the Spanish toxic oil syndrome (TOS) affected more than 20,000 people, and over 300 deaths were registered. Assessment of genetic polymorphisms on xenobiotic metabolism would indicate the potential metabolic capacity of the victims at the time of the disaster. Thus, impaired metabolic pathways may have contributed to the clearance of the toxicant(s) leading to a low detoxification or accumulation of toxic metabolites contributing to the disease. We conducted a matched case-control study using 72 cases (54 females, 18 males) registered in the Official Census of Affected Patients maintained by the Spanish government. Controls were nonaffected siblings (n =72) living in the same household in 1981 and nonaffected nonrelatives (n = 70) living in the neighborhood at that time, with no ties to TOS. Genotype analyses were performed to assess the metabolic capacity of phase I [cytochrome P450 1A1 (CYP1A1), CYP2D6] and phase II [arylamine N-acetyltransferase-2 (NAT2), GSTM1 (glutathione S-transferase M1) and GSTT1] enzyme polymorphisms. The degree of association of the five metabolic pathways was estimated by calculating their odds ratios (ORs) using conditional logistic regression analysis. In the final model, cases compared with siblings (72 pairs) showed no differences either in CYP2D6 or CYP1A1 polymorphisms, or in conjugation enzyme polymorphisms, whereas cases compared with the unrelated controls (70 pairs) showed an increase in NAT2 defective alleles [OR = 6.96, 95% confidence interval (CI), 1.46-33.20] adjusted by age and sex. Glutathione transferase genetic polymorphisms (GSTM1, GSTT1) showed no association with cases compared with their siblings or unrelated controls. These findings suggest a possible role of impaired acetylation mediating susceptibility in TOS.
eng
Pharmacogenetic profile of xenobiotic enzyme metabolism in survivors of the Spanish toxic oil syndrome
research article
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URL
https://repisalud.isciii.es/bitstreams/0aed07de-4b8b-43cc-9178-633dced38d62/download
File
MD5
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application/pdf
PharmacogeneticProfileXenobioticEnzyme_2021.pdf
URL
https://repisalud.isciii.es/bitstreams/a5f06c80-3cb9-4f18-91b1-a6648c7a4b9b/download
File
MD5
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text/plain
PharmacogeneticProfileXenobioticEnzyme_2021.pdf.txt