Tsatsakis A M, Zafiropoulos A, Tzatzarakis M N, Tzanakakis G N, Kafatos A
Centre of Toxicology Sciences and Research, Medical School, University of Crete, Heraklion, Crete, Greece, Voutes, Heraklion, 71409 Crete, Greece.
Toxicol Lett. 2009 Apr 10;186(1):66-72. doi: 10.1016/j.toxlet.2008.10.018. Epub 2008 Oct 28.
Allelic variants of CYP1A1 and PON1 have been extensively studied as susceptibility factors in toxic response, although little is known about the role of these variants as risk factors for the plethora of diseases appearing in the human population. In this study we investigated the hypothesis of correlation of CYP1A1 and PON1 enzymes with the incidence of various medical examination findings in a Greek rural population professionally exposed to a variety of pesticides. The medical history of 492 individuals, randomly selected for the total population of 42,000, was acquired by interviews and their genotype determined for the CYP1A12A, PON1 M/L and PON1 Q/R polymorphisms. The assessment of exposure to pesticides of the population was verified by analytical methods. Analysis of the genetic data revealed that the allele frequencies of PON1 R, M and CYP1A12A alleles were 0.243, 0.39 and 0.107 respectively. The CYP1A1*2A polymorphism was found to have significant association with chronic obstructive pneumonopathy (p=0.045), peripheral circulatory problems (trend p=0.042), arteritis (p=0.022), allergies (trend p=0.046), hemorrhoids (trend p=0.026), allergic dermatitis (p=0.0016) and miscarriages (p=0.012). The PON1 Q/R polymorphism was found to have significant association with hypertension (p=0.046) and chronic constipation (p=0.028) whereas, the L/M polymorphism, with diabetes (p=0.036), arteritis (trend p=0.022) and hemorrhoids (trend p=0.027). Our results demonstrated an association between the CYP1A1/PON1 polymorphisms and several medical examination findings, thus indicating the possible involvement of the human detoxification system to health effects in a rural population exposed professionally to pesticides.
CYP1A1和PON1的等位基因变体作为毒性反应的易感性因素已得到广泛研究，尽管对于这些变体作为人类群体中出现的众多疾病的风险因素的作用知之甚少。在本研究中，我们调查了CYP1A1和PON1酶与希腊农村地区职业性接触多种农药人群中各种医学检查结果发生率之间的相关性假设。通过访谈获取了从42000人的总人口中随机选取的492人的病史，并确定了他们CYP1A12A、PON1 M/L和PON1 Q/R多态性的基因型。通过分析方法验证了该人群农药接触情况的评估。遗传数据分析显示，PON1 R、M和CYP1A12A等位基因的频率分别为0.243、0.39和0.107。发现CYP1A1*2A多态性与慢性阻塞性肺病（p = 0.045）、外周循环问题（趋势p = 0.042）、动脉炎（p = 0.022）、过敏（趋势p = 0.046）、痔疮（趋势p = 0.026）、过敏性皮炎（p = 0.0016）和流产（p = 0.012）有显著关联。发现PON1 Q/R多态性与高血压（p = 0.046）和慢性便秘（p = 0.028）有显著关联，而L/M多态性与糖尿病（p = 0.036）、动脉炎（趋势p = 0.022）和痔疮（趋势p = 0.027）有显著关联。我们的结果表明CYP1A1/PON1多态性与多种医学检查结果之间存在关联，从而表明在职业性接触农药的农村人群中，人体解毒系统可能参与了对健康的影响。
