对氧磷酶及谷胱甘肽S转移酶基因多态性与花卉种植者健康关系分析
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摘要
目的:调查花卉种植者血液中对氧磷酶及谷胱甘肽S转移酶基因多态性的分布情况,并分析评价基因多态性与花卉种植者健康的关系。
     方法:136名种植玫瑰的花农作为暴露组(男74人,女62人);41名不使用农药的当地居民作为对照组(男16人,女25人),进行问卷调查和体格检查,采用聚合酶链反应-限制性多态性法(PCR-RFLP)确定分析对象血液中对氧磷酶启动区-107,编码区192和55位点基因型;谷胱苷肽S转移酶M1、T1的基因型,分析各基因型与乙酰胆碱酯酶(AChE)活力、免疫功能、内分泌水平、临床生化指标、农药接触的症状之间关系。
     结果:
     1、对氧磷酶基因型与农药健康效应
     在全部177名研究对象中,对氧磷酶(PON1)在107位点、192位点和55位点均为多态性分布。基因型分布及等位基因频率性别之间差异无显著性(P>0.05)。
     (1)PON1 107位点
     高暴露组中,TC基因型花农的球蛋白低于TT基因型花农(P<0.05);对于不同暴露组的基因型TC花农:高、低暴露组免疫球蛋白G低于对照组(P<0.01,P<0.05),球蛋白高、低暴露组低于对照组(P<0.05,P<0.05),白球比高、低暴露组高于对照组(P<0.01,P<0.05);睾酮高暴露组低于低暴露组(P<0.05)。
     (2)PON1 192位点
     RR基因型的花农谷丙转胺酶高于QQ基因型的花农(P<0.05),RR、QR基因型的花农天冬氨酸转胺酶高于QQ基因型花农(P<0.01,P<0.05),RR基因型的花农四碘甲状腺原氨酸高于QR基因型的花农(P<0.05);高暴露组中,RR基因型花农四碘甲状腺原氨酸高于QR基因型花农(P<0.05);对于不同暴露的QR基因型花农,睾酮高暴露组高于对照组(P<0.05)。
     (3)PON1 55位点
     控制年龄、性别、吸烟、饮酒等混杂因素之后,各指标无统计学意义(P>0.05)。
     2、谷胱甘肽S转移酶M1、T1基因型与农药接触健康效应
     (1)谷胱甘肽S转移酶M1
     控制年龄、性别、吸烟、饮酒等混杂因素之后,各指标无统计学意义(P>0.05)。
     (2)谷胱甘肽S转移酶T1
     在控制了年龄、性别、吸烟、饮酒、暴露系数后:总蛋白、球蛋白、白球比GSTT1+个体低于GSTT1-花农(P<0.01)、白球比GSTT1+花农高于于GSTT1-花农(P<0.01),IgG GSTT1+花农低于GSTT1-花农(P<0.05),睾酮GSTT1+花农高于GSTT1-花农(P<0.01);高暴露组中,谷草转胺酶、总蛋白、球蛋白GSTT1+花农低于GSTT1-花农(P<0.05)、白球比GSTT1+花农高于GSTT1-花农(P<0.05)、IgA GSTT1+花农高于GSTT1-花农(P<0.05)。
     (3)GSTM1与GSTT1联合分析
     血小板GSTM1+/GSTT1+型花农高于GSTM1-/GSTT1-型花农(P<0.05)。
     3、基因多态和农药接触健康效应的分析
     (1)症状报告与五个基因型logistic回归分析
     年龄越小,相应的不适症状报告越多;GSTM1+者,其症状报告的危险度为GSTM1—者的2.663倍。
     (2)有无心电图异常与五个基因型logistic回归分析
     女性心电异常的危险度为男性的0.496倍。
     4、基因型和细胞凋亡与坏死的关系
     按基因型分组比较细胞凋亡和坏死情况有无差异,经分析,各基因型之间细胞凋亡和坏死率无差异(P>0.05)。
     结论:在全部177名研究对象中,对氧磷酶在107位点、192位点、55位点和GSTM1/T1均为多态性分布。基因型分布及等位基因频率性别之间差异无显著性。
     (1)PON1 107不同基因型,对农药暴露的反应不一样,PON1 107位点可能是农药免疫毒性的易感生物标志物之一。
     (2)PON1 192不同基因型,对农药暴露的反应不一样,PON1 192位点可能是农药内分泌毒性的易感生物标志物之一。
     (3)PON1 55位点不同基因型各指标未见明显的差异。
     (4)谷胱甘肽S转移酶M1+基因型的个体,其症状报告多于GSTM1-基因型的个体,GSTM1基因可能是农药暴露的易感生物标志物之一。
     (5)谷胱甘肽S转移酶T1不同基因型,对农药接触的反应不一样,GSTT1可能是农药免疫、内分泌毒性的易感生物标志物之一。
Objective : To investigate Paraoxonase and Glutathione S-ransferase GenePolymorphism in floriculture, and assess the relationship between gene polymorphismand health condition in floriculturists.
     Methods: 136 pesticide-exposed farmers and 41 local non-pesticide-direct exposedlocals as control. PON1 and GSTM1/T1 genotype were determined by mean ofPolymerase Chain Reaction-Restriction Fragment lengty Polymorphism (PCR-RFLP).Assess if there were associations between genotype and AChE activity、Immunefunction、Endocrinosity、Clinical health index、symptoms.
     Result:
     1、PON1 and health
     In all 177 cases, PON1 regulatory-region-107 and coding region 192 and 55 were polymorphisms.There have no accociation between genotype/alleles frequence and sex.
     (1) PON1-107
     CT genotype is associated with globin in high exposure group (P<0.05) . Compare same genotype CT in different groups, IgG were significant lower in high and low exposure group than in control group(P<0.01, P<0.05) ; Globin were significant lower in high and low exposure group than in control group(P<0.05, P<0.05) ; A/G were significant higher in high and low exposure group than in control group(P<0.01, P<0.05) ; T was significant lower in high exposure group than in low exposure group(P<0.05) .
     (2) PON1 192
     According to different genotypes: ALT in Arg/Arg genotype was higher in Gln/Gln genotype(P<0.05) ; AST in Arg/Arg and Gln/Arg genotype were higher in Gln/Gln genotype(P<0.01,P<0.05) ; T_4 in Arg/Arg genotype was higher in Gln/Arg genotype(P<0.05) ; T_4 Arg/Arg genotype was higher Gln/Arg in high exposure group(P<0.05) ; T Gln/Arg genotype in high exposure group was higher than in control group(P<0.05) .
     (3) PON1 55
     There were no associations between genotype and health index.
     2、GSTM1/T1 and health
     (1) GSTM1
     There were no associations observed between genotype and health index.
     (2) GSTT1
     T GSTT1+ genotype was higher than GSTT1-(P<0.01) ; TP GSTT1+ genotype was lower than GSTT1-(P<0.01) ; GB GSTT1+ genotype was lower than GSTT1-(P<0.01) ; A/G GSTT1+ genotype was higher than GSTT1-(P<0.01) ; IgG GSTT1+ genotype was lower than GSTT1-(P<0.05) ; AST、TP、GB GSTT1+ genotype was lower than GSTT1-in high exposure group(P<0.05) ; A/G GSTT1+ genotype was higher than GSTT1-in high exposure group(P<0.05) ; IgA GSTT1+ genotype was higher than GSTT1-in high exposure group(P<0.05) .
     (3) GSTM1 and GSTT1
     Platet GSTM1+/GSTT1+ genotype was higher than GSTM1-/GSTT1-(P<0.05) .
     3 Gene polymorphism and logistic regression
     The younger the age, The more the symptoms; The persons with GSTM1+, the symptoms were 2.663 times than the persons with GSTM1-.
     Conclusion:
     (1) PON1 107 was a possible susceptibility biomarker the harm of pesticide to immune system;
     (2) PON1 192 was a possible susceptibility biomarker the harm of pesticide to endocrinosity;
     (3) There were no association between PON1 55 genotype and health index;
     (4) The symptoms in GSTM1+ genotype were higher in GSTM1-genotype;
     (5) GSTT1 was a possible susceptibility biomarker the harm of pesticide to immune and endocrinosity system.
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