Tawfik Khattab Amr Mohamed, Zayed Abeer Ahmed, Ahmed Asmaa Ismail, AbdelAal Aly Gamaleldin, Mekdad Alaa AbdelHamid
Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Cairo University, Kasr Al Aini street, Cairo, Egypt.
Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Kasr Al Aini street, Cairo, Egypt.
Neurotoxicology. 2016 Mar;53:102-107. doi: 10.1016/j.neuro.2015.12.015. Epub 2015 Dec 23.
Paraoxonase-1 (PON1) activity toward organophosphorus(OP) compounds shows inter-individual variations, rendering the identification of individuals' PON1 allozymes valuable in treating patients suffering from organophosphorus intoxication. One of the most important cytochrome P450 monooxygenases (CYPs) is CYP2D6. The CYP2D6 G1934A polymorphism leads to good, poor or no enzyme activity. Genetic testing helps identification of high risk individuals as well as management of chronic intoxicated patients.
to investigate a possible association between genetic polymorphisms of PON1 Q192R, and CYP2D6 G1934A as well as PON1 and pseudo-cholinesterase (PChE) enzyme activity levels and chronic organophosphate exposed patients, and hence, susceptibility for organophosphorus chronic poisoning.
Thirty chronic organophosphate exposed farm workers were compared to 29 healthy controls as regards PON1 Q192R and CYP2D6 G1934A polymorphisms using PCR-RFLP technique. Also serum PON1 and PChE activities were determined spectrophotometrically.
Serum PChE was significantly reduced in chronic intoxicated patients compared to the control group (p=0.02), while PON1 activity was increased, but just failed to reach significance (p=0.06). PON1 192 RR genotype and R allele were significantly increased in chronic OP intoxicated patients (p=0.005 &p=0.002 respectively). CYP2D6 1934A allele was significantly increased in chronic OP patients (p=0.045). combining the two SNPs showed a significant statistical difference between the two groups with PON1QQ and CYP2D6 GG genotypes being more represented in the healthy controls (p=0.001). Fatigue and motor weakness were the most prevalent neurological symptoms seen in chronic cases (56.7%), followed by headache and lacrimation (30% each), depression (23%), tingling and sensory symptoms (20%), sleep disorders and limb pain (13%). The mean duration of environmental exposure to organophosphates was 7.7±5.2years and no association was found between chronic symptoms of intoxication and duration of exposure, provided that all workers were exposed for at least 3 years.
PON1 192RR genotype and CYP2D6 1934A allele were found to be related to the susceptibility to organophosphate chronic toxicity in Egyptians. Larger scale gene-environmental interaction studies are recommended to confirm results and Genotyping is recommended during selection of agricultural pesticide workers to exclude high risk group.
对氧磷酶-1（PON1）对有机磷（OP）化合物的活性存在个体差异，这使得鉴定个体的对氧磷酶同工酶对于治疗有机磷中毒患者具有重要价值。最重要的细胞色素P450单加氧酶（CYPs）之一是CYP2D6。CYP2D6 G1934A多态性导致酶活性良好、较差或无活性。基因检测有助于识别高危个体以及管理慢性中毒患者。
研究对氧磷酶-1（PON1）Q192R和细胞色素P450 2D6（CYP2D6）G1934A基因多态性与对氧磷酶（PON1）和假胆碱酯酶（PChE）酶活性水平之间可能存在的关联，以及与慢性有机磷暴露患者的关系，从而确定对有机磷慢性中毒的易感性。
采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术，比较30名慢性有机磷暴露农场工人和29名健康对照者的PON1 Q192R和CYP2D6 G1934A基因多态性。同时用分光光度法测定血清PON1和PChE活性。
与对照组相比，慢性中毒患者血清PChE显著降低（p=0.02），而PON1活性升高，但未达到显著水平（p=0.06）。慢性有机磷中毒患者中PON1 192 RR基因型和R等位基因显著增加（分别为p=0.005和p=0.002）。慢性有机磷患者中CYP2D6 1934A等位基因显著增加（p=0.045）。将两个单核苷酸多态性（SNP）结合起来显示，两组之间存在显著统计学差异，健康对照者中PON1 QQ和CYP2D6 GG基因型更为常见（p=0.001）。疲劳和肌无力是慢性病例中最常见的神经症状（56.7%），其次是头痛和流泪（各30%）、抑郁（23%）、刺痛和感觉症状（20%）、睡眠障碍和肢体疼痛（13%）。有机磷环境暴露的平均持续时间为7.7±5.2年，且未发现中毒慢性症状与暴露持续时间之间存在关联，前提是所有工人暴露时间至少为3年。
发现PON1 192RR基因型和CYP2D6 1934A等位基因与埃及人对有机磷慢性毒性的易感性有关。建议进行更大规模的基因-环境相互作用研究以证实结果，并且建议在选择农业农药工人时进行基因分型以排除高危人群。
