DNA修复基因XRCC1和XRCC3多态性与慢性苯中毒易感性的关系

目的探讨DNA修复基因XRCC1、XRCC3多态性与慢性苯中毒遗传易感性的关联及其与慢性苯中毒潜伏期的关系。方法采用病例-对照研究方法,以确诊并已脱离苯作业的80名慢性苯中毒患者为病例组,以同期接苯的62名苯作业工人为对照组,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析技术,检测XRCC1基因C26304T(Arg194Trp)、G27466A(Arg280His)、G28152A (Arg399Gln)、G36189A(Gln632Gln),位点和XRCC3基因C18067T(Thr241Met)位点的多态性,并采用生存分析方法对慢性苯中毒的潜伏期进行分析。结果携带XRCC3 18067C／T基因型的个体发生慢性苯中毒的危险性低于携带XRCC3 18067C／C基因型的个体(OR=0．233,95％CI:0．085～0．639,P=0．0046);携带XRCC1 27466G／G基因型的个体发生慢性苯中毒的潜伏期比携带27466G／A或A／A基因型的个体长6年。结论在相同的苯作业暴露环境下,携带XRCC3 18067T变异等位基因的个体发生慢性苯中毒的危险性降低;在慢性苯中毒患者中,携带XRCC1 27466 G／G基因型的个体发生慢性苯中毒的潜伏期较长。

Association between genetic polymorphisms of DNA repair genes XRCC1, XRCC3 and susceptibility to chronic benzene poisoning

OBJECTIVE: To explore the association between genetic polymorphisms of DNA repair genes XRCC1, XRCC3 and susceptibility to chronic benzene poisoning. METHODS: A case-control study was conducted. Eighty patients with chronic benzene poisoning and 62 workers occupationally exposed to benzene who were engaged in the same working time and job title as patients were investigated. Polymerase chain reaction-restriction fragments length polymorphism (PCR-RFLP) was used to detect the single nucleotide polymorphisms on C26304T, G27466A, G28152A, G36189A of XRCC1 and C18067T of XRCC3. The relationship between them and latency of chronic benzene poisoning was analyzed by Kaplan-Meier method. RESULTS: A correlation for XRCC3 18067C/T compared with C/C genotype was found (OR=0.233, 95% CI 0.085 approximately 0.639, P=0.0046). Patients who were XRCC1 27466G/G homozygous wild genotype developed chronic benzene poisoning average 6 years later than those had homozygous (27466A/A) or heterozygous (27466G/A) mutant alleles. CONCLUSION: Subjects with XRCC3 18067T variant allele are tolerance sub-group to benzene poisoning. Patients carrying XRCC1 27466 G/G genotype develop chronic benzene poisoning later.