Veterans Health Research Program, Yudofsky Division of Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Medicine (Division Medical Genetics), University of Washington, Seattle, WA 98195, USA.
Int J Environ Res Public Health. 2024 Jul 24;21(8):964. doi: 10.3390/ijerph21080964.
Deployment-related neurotoxicant exposures are implicated in the etiology of Gulf War illness (GWI), the multisymptom condition associated with military service in the 1990-1991 Gulf War (GW). A Q/R polymorphism at position 192 of the paraoxonase (PON)-1 enzyme produce PON1 variants with different capacities for neutralizing specific chemicals, including certain acetylcholinesterase inhibitors.
We evaluated PON1 status and GW exposures in 295 GWI cases and 103 GW veteran controls. Multivariable logistic regression determined independent associations of GWI with GW exposures overall and in PON1 subgroups. Exact logistic regression explored effects of exposure combinations in PON1 subgroups.
Hearing chemical alarms (proxy for possible nerve agent exposure) was associated with GWI only among RR status veterans (OR = 8.60, = 0.014). Deployment-related skin pesticide use was associated with GWI only among QQ (OR = 3.30, = 0.010) and QR (OR = 4.22, < 0.001) status veterans. Exploratory assessments indicated that chemical alarms were associated with GWI in the subgroup of RR status veterans who took pyridostigmine bromide (PB) (exact OR = 19.02, = 0.009) but not RR veterans who did not take PB (exact OR = 0.97, = 1.00). Similarly, skin pesticide use was associated with GWI among QQ status veterans who took PB (exact OR = 6.34, = 0.001) but not QQ veterans who did not take PB (exact OR = 0.59, = 0.782).
Study results suggest a complex pattern of PON1 exposures and exposure-exposure interactions in the development of GWI.
与部署相关的神经毒性剂暴露与海湾战争病（GWI）的病因有关，GWI 是与 1990-1991 年海湾战争（GW）期间军事服役相关的多症状疾病。位于对氧磷酶（PON）-1 酶的 192 位的 Q/R 多态性产生了具有不同中和特定化学物质能力的 PON1 变体，包括某些乙酰胆碱酯酶抑制剂。
我们评估了 295 例 GWI 病例和 103 例 GW 退伍军人对照者的 PON1 状况和 GW 暴露情况。多变量逻辑回归确定了 GWI 与 GW 暴露的总体和 PON1 亚组之间的独立关联。精确逻辑回归探索了 PON1 亚组中暴露组合的影响。
听觉化学警报（可能神经毒剂暴露的代表）仅与 RR 状态退伍军人的 GWI 相关（OR = 8.60， = 0.014）。与 Deployment 相关的皮肤杀虫剂使用仅与 QQ（OR = 3.30， = 0.010）和 QR（OR = 4.22， < 0.001）状态退伍军人的 GWI 相关。探索性评估表明，化学警报与 RR 状态退伍军人中服用溴吡斯的明（PB）的亚组的 GWI 相关（确切 OR = 19.02， = 0.009），但与未服用 PB 的 RR 退伍军人无关（确切 OR = 0.97， = 1.00）。同样，皮肤杀虫剂的使用与 QQ 状态退伍军人中服用 PB 的亚组的 GWI 相关（确切 OR = 6.34， = 0.001），但与未服用 PB 的 QQ 退伍军人无关（确切 OR = 0.59， = 0.782）。
研究结果表明，PON1 暴露和暴露-暴露相互作用在 GWI 的发展中存在复杂的模式。
