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Gulf War and Health: Volume 1. Depleted Uranium, Sarin, Pyridostigmine Bromide, Vaccines
likely to be classified as having one of six new proposed syndromes (Haley et al., 1997; see also Chapter 2). Specifically, this syndrome—labeled by the investigators as “confusion–ataxia” or “syndrome 2”—features problems with thinking, disorientation, balance disturbances, vertigo, and impotence. This was the only syndrome of the six to have been associated with self-reported chemical weapons exposure (see Chapter 6).
A follow-up study of vestibular function was performed on a subset of those veterans (n = 23) who had the highest factor scores on three of the syndromes identified in 1997 by Haley and Kurt (Roland et al., 2000). The study was designed to probe the nature of veterans’ vestibular symptoms, rather than to examine the relationship between vestibular performance and exposure in the Gulf War. Of the 23 veterans in this study, 13 exhibited syndrome 2, whereas the others exhibited syndromes 1 (impaired cognition) and 3 (arthromyoneuropathy) (see Chapter 2). Based on a new questionnaire, veterans with syndrome 2 reported dizzy spells with greater frequency and longer duration than veterans with the other two syndromes. Veterans with syndrome 3, but not syndrome 2, performed significantly differently from controls on dynamic platform posturography (a test similar to that used by Japanese researchers to identify impairment in sarin-exposed females; see Yokoyama et al., 1998a). Veterans with other syndromes also had performance decrements on some of the measures of vestibular function. The study concluded that there was both subjective and objective evidence of injury to the vestibular system in this group of Gulf War veterans with newly defined syndromes. Haley and Kurt (1997) hypothesized that these newfound chronic syndromes represent variants of OPIDN caused by exposure to various combinations of organophosphates (pesticides and nerve agents) and carbamate pesticides that inhibit cholinesterases and NTE (see Chapters 2 and 6).
Genetic Susceptibility to Sarin Toxicity
One of the mechanisms of sarin inactivation is by hydrolysis with the enzyme paraoxonase (PON1), an esterase found in liver and serum. The human PON1 gene has polymorphisms at positions 192 (Arg/Gln) and 55 (Leu/Met) (Furlong et al., 1993). The former accounts for three genotypes (QQ, RR, and QR) relating to the catalytic properties of two forms of an enzyme (types R and Q allozymes), which hydrolyze certain organophosphates at different rates. The R allozyme (Arg192) hydrolyzes the organophosphate paraoxon at a high rate; however, it has a low activity toward OP nerve agents such as sarin and soman (Davies et al., 1996). Lower activity means that more sarin would be bioavailable to exert its anticholinesterase effects. The Q allozyme, on the other hand, has high activity toward organophosphate nerve agents (and low activity toward paraoxon). Thus, individuals with the Q allozyme (QQ or QR) are expected to have greater hydrolysis of sarin than individuals homozygous for the R allele (RR). Since hydrolytic activity with the same genotype can vary about tenfold, it is also important to determine the level of allozyme expression—in addition to