CYP2E1基因拷贝数多态性与职业性铅中毒易感性的关系研究

Relationship between occupational lead poisoning susceptibility and copy number variations of CYP2E1 gene

目的探讨生物代谢Ⅰ相酶CYP2E1基因拷贝数多态性与铅中毒的关系。方法按性别分层后,采用简单随机抽样方法选取2007—2009年间某市蓄电池行业200名触铅作业人员作为研究对象,采用统一调查表问卷调查工人的基本情况、职业史及相关自觉症状和临床体征情况;采用石墨炉原子吸收光谱法测定调查对象血铅、尿铅水平;采用实时荧光定量PCR法和ΔCt值法检测200名铅接触工人的CYP2E1基因拷贝数。采用方差分析方法分析不同CYP2E1基因拷贝数之间血铅、尿铅含量的不同;采用2检验和多因素logistic回归分析不同CYP2E1基因拷贝数各组之间自觉症状和临床体征频率分布的不同。结果 200名铅作业工人中,男性101人(50.5%),女性99人(49.5%),平均年龄(37.63±6.97)岁。CYP2E1基因拷贝数0、1、2组在年龄、工龄、学历及工种方面的差异均无统计学意义(均P>0.05),在性别方面的差异处于临界状态(P=0.04);CYP2E1基因拷贝数0、1、2组的血铅水平分别为(2.81±0.81)、(2.31±0.93)、(2.32±0.75)μmol/L,调整了年龄、性别、工龄、学历、工种等混杂因素后,拷贝数为0组的血铅浓度明显高于拷贝数为1、2组(P<0.05)。CYP2E1基因拷贝数0、1、2各组出现头昏乏力、腹痛、四肢麻木、肌肉酸痛等相关自觉症状的频率分别为44.0%(11/25)、25.0%(16/64)及22.5%(25/111),差异无统计学意义(P>0.05)。CYP2E1基因拷贝数0、1、2各组的临床体格检查出现腹部压痛、周围神经反射改变等阳性率分别为16.0%(4/25)、7.8%(5/64)及2.8%(3/108),差异有统计学意义(P<0.05)。进一步采用多因素logistic回归分析调整上述各种混杂因素的影响,发现基因拷贝数为0者出现阳性体征的风险是其他基因型者的4倍左右(OR=4.10)。结论 CYP2E1基因拷贝数多态性与触铅作业人员的铅中毒程度可能有关,CYP2E1基因拷贝数为0可能是铅中毒的易感基因型。

Objective To probe into the relationship between lead poisoning susceptibility and copy number variations of CYP2E1 gene. Methods Workers exposed to lead in a battery factory were re- cruited by gender stratification from 2007 to 2009. Then they were scheduled for interviews to collect the data on occupational information. Their blood and urine lead were tested using graphite furnace atomic ab- sorption spectrometry, and the copy number of CYP2E1 gene were detected by real-time fluorescence quan- titative PCR and ACt method. The blood and urine lead levels in subjects with different genotypes were analyzed by ANOVA, and their symptoms and physical signs were analyzed using ehi-square and logistic re gression tests. Results Of 200 cases recruited in this study, 101 were males （50.5%） and 99 were females （49.5 % ）, with average age of （37.63 ± 6.97 ） years. The genotype distributions of CYP2E1 did not significantly differ among subgroups of age, education, length of service, and occupation （P 〉 0.05 for all）, and showed borderline significance between different sexes （P = 0.04）. Different CYP2E1 gene copy numbers had different blood lead levels [ （2.81 ±0.81 ） μmol/L for zero copy, （2.31 ±0.93） μmol/L for one copy, and （2.32 ± 0.75） μmol/L for two copies ] , and the differences were statistically significant after adjusting age, sex, education, length of service, and occupation （ P 〈 0.05 ）. The frequencies of related symptoms, such as dizzy, bellyache, and limb numbness, in cases with different genotypes were 44.0% （ 11/25）, 25.0% （ 16/64 ） and 22.5% （ 25/111 ）, respectively, without significant difference （ P 〉 0. 05）. However, the frequencies of related physical signs, such as abdominal tenderness and changes of peripheral nervous reflex, were significantly different in cases with different genotypes [ 16.0% （4/25）for zero copy, 7.8% （5/64） for one copy, and 2.7% （3/108） for two copies, P 〈0.05]. After adjusting confounding factors, the cases with zero copy had 4 fold risk for related physical signs compared to other genotypes （adjusted OR = 4.10）. Conclusion Copy number variations of CYP2E1 gene may be related with the degree of lead poisoning, and the zero copy genotype of CYP2E1 might be susceptible to lead poisoning.