Genetic polymorphisms and activity of PON1 in a Mexican population

Journal Article · Wed Jun 15 04:00:00 EDT 2005 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2004.10.015· OSTI ID:20721827

Rojas-Garcia, A E ^[1]; Solis-Heredia, M J ^[1]; Pina-Guzman, B ^[1]; Vega, L ^[1]; Lopez-Carrillo, L ^[2]; Quintanilla-Vega, B ^[1]

---

1. Seccion Externa de Toxicologia, CINVESTAV-IPN, PO Box 14-740, Mexico City, 07300 (Mexico)
2. Instituto Nacional de Salud Publica, Ave. Universidad No. 655, Col. Santa Ma. Ahuacatitlan, Cuernavaca, Mor., 62508 (Mexico)

Human paraoxonase (PON1) plays a role in detoxification of organophosphorus (OP) compounds by hydrolyzing the bioactive oxons, and in reducing oxidative low-density lipoproteins, which may protect against atherosclerosis. Some PON1 polymorphisms have been found to be responsible for variations in catalytic activity and expression and have been associated with susceptibility to OP poisoning and vascular diseases. Both situations are of public health relevance in Mexico. Therefore, the aim of this study was to evaluate PON1 phenotype and the frequencies of polymorphisms PON1 -162, -108, 55, and 192 in a Mexican population. The studied population consisted of unrelated individuals (n = 214) of either gender, 18-52 years old. Serum PON1 activity was assayed using phenylacetate and paraoxon as substrates. PON1 variants, -162, 55, and 192, were determined by real-time PCR using the TaqMan System, and PON1 -108 genotype by PCR-RFLP. We found a wide interindividual variability of PON1 activity with a unimodal distribution; the range of enzymatic activity toward phenylacetate was 84.72 to 422.0 U/mL, and 88.37 to 1645.6 U/L toward paraoxon. All four PON1 polymorphisms showed strong linkage disequilibrium (D% >90). PON1 polymorphisms -108, 55, and 192 were independently associated with arylesterase activity; whereas the activity toward paraoxon was related only with PON1 192 polymorphism, suggesting that this polymorphism is determinant to infer PON1 activity. A better understanding of the phenotype and genotypes of PON1 in Mexican populations will facilitate further epidemiological studies involving PON1 variability in OP poisoning and in the development of atherosclerosis.

• OSTI ID: 20721827
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 205; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ARTERIOSCLEROSIS
DETOXIFICATION
GENOTYPE
LIPOPROTEINS
METABOLISM
PESTICIDES
PHENOTYPE
POISONING
POLYMERASE CHAIN REACTION
PUBLIC HEALTH