MPO、NQO1、GSTP1和UGT1A6基因多态与慢性苯中毒遗传易感性关系

目的探讨MPO、NQO1、GSTP1和UGT1A6基因多态与慢性苯中毒易感性的关系。方法采用病例-对照研究,以268名苯中毒工人为病例组,268名接触苯而没有中毒表现的工人为对照组。应用TaqManPCR分析技术判定MPO(rs7208693),NQO1(rs1800566),GSTP1(rs947894)和UGT1A6(rs6759892,rs1105879,rs4124874,rs3755319,rs887829和rs4148323)基因型。结果携带GSTP1基因rs947894G等位基因个体患慢性苯中毒的危险性比AA基因型个体降低0.657倍(95%CI0.434~0.994,P=0.046);携带MPO基因rs7208693A等位基因人群中,UGT1 A6 rs6759892G等位基因个体发生慢性苯中毒的危险性是TT基因型的2.702倍(P=0.024),UGT1 A6 rs1105879C等位基因个体发生慢性苯中毒的危险性是TT型的2.619倍(P=0.035)。在饮酒人群中,携带NQO1基因rs1800566TT基因型个体慢性苯中毒的发病风险较携带CC和CT基因型个体增加9.000倍(95%CI1.460~55.478,P=0.021);在吸烟人群中,带NQO1基因rs1800566TT基因型个体慢性苯中毒的发病风险较携带CC和CT基因型个体增加7.000倍(95%CI1.555~31.575,P=0.012)。单倍型分析显示,本人群携带UGT1A6基因TACGGG单倍型个体慢性苯中毒的发病风险是携带TAATGG单倍型个体的1.446倍(OR=1.446,95%CI1.005~2.080,P=0.046)。结论同时携带MPO基因rs7208693A和UGT1A6基因rs6759892G或rs1105879C等位基因型个体对苯中毒易感;携带NQO1基因rs1800566TT基因型且同时吸烟或饮酒的个体对苯中毒易感;携带UGT1A6基因TAATGG单倍型个体可增加慢性苯中毒的发病风险;GSTP1基因多态与慢性苯中毒遗传易感性的关系仍需进一步研究。

Genetic polymorphisms of MPO, NQO1, GSTP1, UGT1A6 associated with susceptibility of chronic benzene poisoning

Objective To explore the relationship between genetic polymorphisms in MPO, NQO1, GSTP1, UGT1A6 and susceptibility to chronic benzene poisoning (BP). Methods A case-control study was conducted. 268 BP patients and 268 workers occupationally exposed to benzene without poisoning manifestations were investigated. The genotype of MPO(rs7208693), NQO1 (rs1800566), GSTP1(rs947894) and UGT1A6(rs6759892,rs1105879,rs4124874,rs3755319,rs887829 and rs4148323) were tested by the TaqMan PCR method. Results There was a 0.675-fold (95%CI 0.434-0.994, P=0.046) decreased risk of BP in the subjects with GSTP1 rs947894 G alleles compared with those carrying AA genotype. In the subjects carrying allele of MPO rs7208693 A, the risk of BP increased for the individuals carrying allele of UGT1A6 rs6759892 G (OR=2.702,P=0.024) compared to those with TT genotype or the individusals carrying allel of UGT1A6 rs1105879 C (OR=2.619, P=0.035) compared to those with TT genotype. In drinking population, the individuals carrying the NQO1 rs1800566 TT homozygote genotype had a 9.000-fold (5%CI 1.460-55.478,P=0.021) risk of BP compared to those with CT CC genotypes. In smoking population, there was 7.000-fold (95%CI 1.555-31.575,P=0.012) of risk in BP subjects carrying NQO1 rs1800566T/T genotype, compared with those carrying CC CT genotype. Haplotyes analysis of polymorphisms in UGT1A6 showed that compared with those carrying TAATGG haplotype, there was a 1.446-fold (OR=1.446,95%CI 1.005-2.080,P=0.046) increased risk of BP for those carrying TACGGG haplotype. Conclusion The subjects carrying allele of MPO rs7208693 A and UGT1A6 rs6759892 G or rs1105879 C at the same time could be more susceptible to BP. The subjects carrying NQO1 rs1800566 TT genotype and together with the habit of smoking or drinking could be more susceptible to BP. Those subjects carrying TAATGG haplotype of UGT1A6 could increase the risk of BP. Further studies should be needed on the association between the genetic polymorphisms in GSTP1 and the risk of BP.