XRCC1、hOGG1和MGMT基因多态性与氯乙烯接触工人染色体损伤的关系
XRCC1, hOGG1 and MGMT Genetic Polymorphisms and Chromosomal Damage in Vinyl ChlorideExposed Workers
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摘要:
目的 探讨DNA损伤修复基因X线修复交叉互补基因1(X-ray repair cross complementing gene 1,XRCC1)、人8-羟基鸟苷糖苷酶1基因(human 8-oxoguanine DNA glycosylase-1,hOGG1)以及O6-甲基鸟嘌呤-DNA甲基转移酶基因(O6-methyl-guanine DNA methyltransferase,MGMT))的多态性与氯乙烯致人外周血淋巴细胞染色体损伤的关系。 方法 采用胞质阻滞微核试验方法(CBMN)评价313名氯乙烯接触工人和141名对照工人染色体损伤水平,应用聚合酶链反应-限制性片段多态性技术(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)对接触工人XRCC1基因Arg194Trp、Arg280His和Arg399Gln 3个位点和hOGG1基因Ser326Cys位点及MGMT基因Leu84Phe位点进行多态性检测。采用SAS软件包进行统计分析,计算率比(frequency ratio,FR)及其95%可信限(95% confidence interval,95%CI)。 结果 本研究表明,氯乙烯接触工人的微核率为(4.86& #177;2.80)‰,显著高于对照人群的微核率(1.22& #177;1.24)‰(P<0.01)。携带hOGG1 326 Ser/Cys基因型(FR=1.21,95%CI:1.02~1.46;P<0.05)、XRCC1 194 Arg/Trp基因型(FR=1.12,95%CI:1.00~1.25;P<0.05)和XRCC1 280 Arg/His和His/His基因型(FR=1.12,95%CI:1.00~1.26;P<0.05)的个体均易发生染色体损伤。在易感性的双体型中,携带CGA/CAG的个体相比携带野生型CGG/CGG的个体微核率明显升高(FR=1.67,95%CI:1.19~2.23;P<0.05)。接触组人群的微核率随着年龄的增长显著升高(FR=1.13,95%CI:1.00~1.28;P<0.05)。对XRCC1基因型进行联合分析,发现随着剂量增加和携带突变等位基因数目增多,其染色体损伤风险增大。 结论 胞质阻滞微核可以作为氯乙烯接触工人早期健康损害的敏感指标,基因型XRCC1 Arg194Trp、Arg280His、hOGG1 Ser326Cys和双体型CGA/CAG以及年龄增长可能对氯乙烯致工人染色体损伤的过程产生影响。氯乙烯累积接触水平与XRCC1基因型也可能存在一定的交互作用。 Abstract:Objective To explore the relationship between genetic polymorphism of x-ray repair cross complementing gene 1 (XRCC1), human 8-oxoguanine DNA glycosylase-1 (hOGG1) and O6-methylguanine DNA methyltransferase (MGMT)) and susceptibility of chromosomal damage induced by vinyl chloride monomer (VCM). Methods A total of 313 workers occupationally exposed to VCM and 141 normal individuals were involved. Cytokinesis-block micronucleus (CBMN) assay was used to detect chromosome damage in peripheral lymphocyte. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was applied to detect polymorphisms in XRCC1 (Arg194Trp, Arg280His, Arg399Gln), MGMT (Leu84Phe) and hOGG1 (Ser326Cys) of the exposed workers. Statistical analysis was performed using SAS software to calculate frequency ratio (FR) and 95% confidence interval (95%CI). Results The micronucleus (MN) frequency of the exposed workers(4.86& #177;2.80) ‰ was significantly higher than that of the controls(1.22& #177;1.24)‰(P<0.01). Workers who carried the hOGG1 326 Ser/Cys genotype (FR=1.21, 95%CI:1.02-1.46; P<0.05), the XRCC1 194 Arg/Trp genotype (FR=1.12, 95%CI:1.00-1.25; P<0.05), and the XRCC1 280 Arg/His and His/His genotypes (FR=1.12, 95%CI:1.00-1.26; P<0.05) were more susceptible to chromosome damage. Moreover, among susceptibility diplotypes, CGA/CAG carriers had more risks of MN frequency compared with individuals with wild-type CGG/CGG (FR=1.67, 95%CI:1.19-2.23; P<0.05). Among the exposed workers, the MN frequency also increased significantly with age (FR=1.13, 95%CI:1.00-1.28; P<0.05). In addition, the higher exposure level was and the more number of allele genes in XRCC1 were, the more serious chromosome damage in VCM exposed workers would be. Conclusion CBMN may be used as a sensitive index to early damage in VCM exposed workers. Genotype XRCC1 Arg194Trp, Arg280His, hOGG1 Ser326Cys, diplotype CGA/CAG and age may have effects on the chromosome damage induced by VCM. Exposure level and genotype of XRCC1 may have interaction effects.
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