Hotopf Matthew, Mackness Michael Ian, Nikolaou Vasilis, Collier David A, Curtis Charles, David Anthony, Durrington Paul, Hull Lisa, Ismail Khalida, Peakman Mark, Unwin Catherine, Wessely Simon, Mackness Bharti
Gulf War Research Unit, King's College London, 103 Denmark Hill, London SE5 8AZ, UK.
J Occup Environ Med. 2003 Jul;45(7):668-75. doi: 10.1097/01.jom.0000071506.96740.39.
Serum paraoxonase (PON1) is responsible for the metabolism of organophosphates in serum, and PON1 activity is a major determinant of their toxicity in humans. There have been reports linking lowered PON1 activity to physical symptoms after deployment to the Persian Gulf War (PGW) of 1990 to 1991. Therefore, the object of this study was to determine (1) whether PON1 activity was decreased among symptomatic PGW veterans compared with asymptomatic PGW veterans and (2) to determine whether PGW veterans as a whole had lower PON1 activity compared with other military control groups. This was a case control study nested in occupational cohort study of military personnel. Four groups of military personnel were identified from a large epidemiological study of health effects of deployment to the PGW and Bosnia: (1) symptomatic PGW veterans, n = 115; (2) healthy PGW veterans, n = 95; (3) symptomatic Bosnia peacekeeping veterans, n = 52; and (4) symptomatic nondeployed military controls, n = 85. The main outcome measures were PON1 activity and genotype for PON1-55 and -192. We found significant differences in PON1 activity among these four groups, and although the two Gulf groups did not differ in PON1 activity, those deployed to the Gulf had significantly lower PON1 activity compared with the non-PGW groups (median difference = 70.9; 95% CI: 20.2, 121.5, P = 0.012). These differences were not explained by a range of potential confounders, or differences in PON1 coding region polymorphisms. PON1 activity is reduced in PGW veterans compared with military control groups. The effect is independent of ill health in PGW veterans.
血清对氧磷酶(PON1)负责血清中有机磷酸酯的代谢,PON1活性是其对人类毒性的主要决定因素。有报告称,1990年至1991年海湾战争(PGW)退伍军人中,PON1活性降低与身体症状有关。因此,本研究的目的是确定:(1)有症状的PGW退伍军人与无症状的PGW退伍军人相比,PON1活性是否降低;(2)与其他军事对照组相比,PGW退伍军人整体的PON1活性是否较低。这是一项嵌套在军事人员职业队列研究中的病例对照研究。从一项关于海湾战争和波斯尼亚部署对健康影响的大型流行病学研究中确定了四组军事人员:(1)有症状的PGW退伍军人,n = 115;(2)健康的PGW退伍军人,n = 95;(3)有症状的波斯尼亚维和退伍军人,n = 52;(4)有症状的未部署军事对照组,n = 85。主要观察指标为PON1活性以及PON1 - 55和 - 192的基因型。我们发现这四组之间的PON1活性存在显著差异,尽管两个海湾组的PON1活性没有差异,但与非PGW组相比,部署到海湾地区的人员PON1活性显著降低(中位数差异 = 70.9;95% CI:20.2,121.5,P = 0.012)。这些差异无法用一系列潜在混杂因素或PON1编码区多态性差异来解释。与军事对照组相比,PGW退伍军人的PON1活性降低。这种影响与PGW退伍军人的健康状况不佳无关。