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目的探讨细胞周期调控基因P53、P21和细胞周期蛋白D1基因多态与氯乙烯致外周血淋巴细胞染色体损伤易感性的关系。方法采用胞质分裂阻滞微核试验方法评价183名氯乙烯接触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对P53第4外显子、第3和6内含子,P21第2外显子和第3外显子的3′非翻译区,以及CCND1基因第4外显子等多态位点进行检测。结果研究对象P53基因第4外显子,第3和6内含子等位基因的突变频率分别为0.45,0.04,0.05,P21第2外显子和第3外显子两个位点的突变频率分别为0.37和0.50,CCND1第4外显子突变频率为0.42。多因素Poisson回归分析结果表明,30岁以上年龄组的人群发生染色体损伤的危险度是30岁以下年龄组人群的1.2202倍,差异有统计学意义(OR=1.2202,95%CI:1.0580～1.4072,P=0.0062);女性发生染色体损伤的危险度是男性的1.1491倍,差异有统计学意义(OR=I.1491,95%CI:0.9841～1.3416,P=0.0772);P53第6内含子突变基因型人群发生染色体损伤的危险度是野生基因型人群的1.3032倍,差异有统计学意义(OR=1.3032,95%CI:1.1285～1.6405,P=0.0285)。P53单倍型分析结果表明,携带BBB/AAA和BAB/AAA单倍型对(按照P53第4外显子、第3和6内含子顺序,B表示突变型,A表示野生型)的人群微核率与野生型AAA/AAA人群相比,OR值分别为1.4418(95%CI:1.0316～2.0152)和1.7100(95%CI:1.0385～2.8157)。结论氯乙烯暴露人群中,30岁以上、女性、P53 INTRON6等位基因突变以及P53第4外显子,第3和第6内含子单倍型对为BBB/AAA和BAB/AAA都是个体发生染色体损伤的危险因素。
Objective To investigate the relationship between the polymorphisms of P53, P21 and cyclin D1 and the susceptibility to chromosome damage induced by vinyl chloride in peripheral blood lymphocytes. Methods Cytokinesis of micronucleus test was used to evaluate the level of chromosomal damage in 183 workers exposed to vinyl chloride. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the expression of exon 4, , P21 exon 2 and exon 3 of the 3 ’untranslated region, as well as CCND1 gene exon 4 and other polymorphic sites were detected. Results The mutation frequencies of exon 4, 3 and 6 in P53 gene were 0.45, 0.04 and 0.05, respectively. The mutations of exon 2 and exon 3 in P21 The frequencies were 0.37 and 0.50, respectively, and the frequency of the fourth exon CCND1 mutation was 0.42. The results of multivariate Poisson regression analysis showed that the risk of chromosomal damage in people over 30 years old was 1.2202 times of the age group below 30 years old, the difference was statistically significant (OR = 1.2202, 95% CI: 1.0580-1.4072, P = 0.0062). The risk of chromosomal damage in females was 1.1491 times of that in males (OR = I.1491, 95% CI: 0.9841 ~ 1.3416, P = 0.0772) The risk of chromosomal damage in genotypes was 1.3032 times higher than that in wild genotypes (OR = 1.3032, 95% CI: 1.1285-1.6405, P = 0.0285). P53 haplotype analysis showed that the population carrying BBB / AAA and BAB / AAA haplotype pairs (mutant according to P53 exon 4, introns 3 and 6, B representing mutant, and A representing wild type) The ORs of micronucleus rate and wild type AAA / AAA population were 1.4418 (95% CI: 1.0316-2.0152) and 1.7100 (95% CI: 1.0385-2.8157), respectively. CONCLUSIONS: Among individuals exposed to vinyl chloride, mutations in the P53 INTRON6 allele and P53 exon 4, with haplotypes BBB / AAA and BAB / AAA in individuals over the age of 30, are all individuals Risk factors for chromosomal damage.