PON1 Status and Neurologic Symptom Complexes in Gulf War Veterans
- Departments of Genetics and Medicine, University of Washington, Seattle, Washington 98195-7360 USA
This extract was created in the absence of an abstract.
In a case of potential exposure to toxic chemicals, it is often difficult to dissect the genetic, physiological, and environmental factors that contribute to illness. A recently published paper (Haley et al. 1999) raises the possibility of a link between detoxication enzyme genotype/phenotype and the risk of illness in Gulf War veterans. This work builds on a body of interesting data regarding detoxication enzyme polymorphisms and highlights the need to consider both genotypic and phenotypic information in epidemiological studies.
Haley et al. (1997) had previously identified six unique symptom complexes, which they suggested could represent neurologic syndromes or injury sustained in the Gulf War. In the present study (Haley et al. 1999), they examined the relationship of polymorphisms in the paraoxonase gene (PON1) to presentation of neurologic symptom complexes in Gulf War veterans. Paraoxonase (PON1) is a high density lipoprotein (HDL)-associated enzyme that metabolizes oxidized lipids and also hydrolyzes arylesters and a number of toxic organophosphorus (OP) compounds, including insecticides and nerve agents (Aldridge 1953b; Geldmacher-von Mallinckrodt and Diepgen 1988; Davies et al. 1996). Haley et al. (1999) found that veterans homozygous for a specific PON1 allele (PON1 Q192) were less likely to have neurologic symptom complexes than those possessing the alternate allele (PON1 R192). They also noted that low activity of the plasma PON1Q192 isoform distinguished ill veterans from controls even better than the PON1 genotype. According to Haley et al. (1999), these results support the contention that Gulf War-related neurologic syndromes were caused by exposure to toxic chemical compounds.
Do their conclusions seem to be justified based on what is known about the human PON1192 protein polymorphism? Ideally, in an OP exposure scenario, the parameters that would be useful for an epidemiological study are (1) an identification of the compounds to which the …
