CYP2D6和UGT1A6基因多态性与慢性苯中毒的危险性

Association of Genetic Polymorphism of CYP2D6 and UGT1A6 with Risks of Chronic Benzene Poisoning

目的探讨CYP2D6基因和UGT1A6基因多态性与慢性苯中毒易感性的关系.方法采用病例一对照研究,选择152名苯中毒工人为病例组,152名接触苯而无中毒表现的工人为对照组.采用PCR-RFLP技术检测CYP2D6第9外显子g.4268位点和UGT1A6第1外显子t.181位点的多态性.结果携带CYP2D6 g.4268 C/C基因型的个体较携带有CYP2D6 g.4268 G/G或G/C基因型的个体发生苯中毒的危险性高1.72倍(95%CI:1.8～2.78,P=0.03);在不吸烟的人群中,携带CYP2D6 g.4268 C/C基因型的个体比携带G/G或G/C基因型的个体发生苯中毒的风险性高1.75倍(95%CI:1.03～2.94,P=0.04);在不饮酒的人群中,携带CYP2D6 g.4268 C/C基因型个体比携带CYP2D6 g.4268 G/G和G/C基因型的个体发生苯中毒的危险性高1.82倍(95%CI:1.09～3.03,P=0.02).UGT1A6 t.181的各基因型在病例组和对照组的分布频率差异无显著性(P＞0.05).结论携带CYP2D6 g.4268 C/C基因型的个体对苯中毒可能易感.

Objective To explore the association of genetic polymorphisms of CYP2D6 and UGT1A6 with risks of chronic benzene poisoning(BP).Methods A case-control study was conducted in 152 BP patients and 152 benzene-exposed workers with no poisoning manifestations.Polymerase chain reaction followed by restriction fragment length polymorphism(PCR-RFLP)technology were used to detect the single nucleotide polymorphisms of g.4268 position in the ninth extron of CYP2D6 gene and t.181 position in the first extron of UGT1A6 gene.Results The individuals carrying CYP2D6 g.4268 C/C genotype had a 1.72-fold(95% CI:1.08～2.78,P=0.03)increased risk of BP compared with those carrying G/G and G/C genotypes.In non-smoking population,there was a 1.75-fold(95% CI:1.03～2.94,P=0.04)increased risk of BP for subjects carrying CYP2D6 g.4268 C/C genotype compared with those carrying G/G and G/C genotypes,and in non-drinking population,the individuals carrying CYP2D6 g.4268 C/C genotype had a 1.82-fold(95% CI:1.09～3.03,P=0.02)increased risk compared with those carrying G/G and G/C genotypes.There is no statistical significance in the distribution of genotypes of UGT1A6 t.181(P>0.05)between case and control groups.Conclusions It was suggested that the individuals carrying CYP2D6 g.4268 C/C genotype might be more susceptible to BP.