细胞色素P450 1A1和2D6基因多态性与慢性苯中毒的危险性

Genetic polymorphism of CYP-1A1, CYP2D6 and risks of chronic benzene poisoning

目的探讨细胞色素P450 1A1和2D6基冈多态性与慢性苯中毒易感性的关系。方法采用病例-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。采用限制性片段聚合酶链反应(PCR—RFLP)技术榆测CYP1A1基因3’端非编码区Msp I和CYP2D6第1外显子c．188位点、g．212位点多态性。结果携带CYP1A1 Msp I T／T基因型的个体发生苯中毒的危险性是携带有CYP1A1 Msp I T／C或C／C基因型的个体的1．32倍(95％CI:1．05～1．65, P=0．02);在不吸烟的人群中,携带CYP1A1 Msp I T/T基因型的个体发生苯中毒的风险性是携带T/C或C／C基因型的个体的1．56倍(95％CI:1．15～2．12,P=0．003);携带有CYP2D6 c．188 C／C或C／T基因型个体发生苯中毒的危险性足携带有CYP2D6 c．188 T/T基因型的个体的1．23倍(95％CI:1．05～1．42,P=0．01),在不吸烟的人群中,携带CYP2D6 c．188 C／C或C/T基因型个体发生苯中毒的危险性是携带有CYP2D6 c．188 T／T基因型的个体的1．23倍(95％CI:1．04～1．47,P=0．01)。未发现研究对象的CYP2D6g．212位点存在多态性。结论携带CYP1A1 Msp J T/T基因型、CYP2D6 c．188 C／C和C/T基因型个体对苯中毒可能易感。

Objective To explore the relationship between genetic polymorphisms of CYP-IAI and CYP2D6 and risks of chronic benzene poisoning（ BP）. Methods A case control study was conducted. 152 BP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were involved. Polymerase chain reaction followed by restriction fragment length polymorphism（PCR-RFLP） technology was used for detecting the single nucleotide polymorphisms（SNPs）of Msp 1 in the non-coding region of CYP-IAI gene and c. 188, g. 212 position in the first extron of CYP2D6 gene. Results The individuals with CYPIA 1 Msp [ T/T genotype had a 1.32 times（95% CI：I .05 - 1.65, P = 0.02） increased risk of BP compared with those carr）, ing T/C and C/C genotypes.In no-smoking population, there was a 1.56 times（95% CI： 1.15 - 2.12, P = 0.003）increased risk of BP for subjects carrying CYPIAI Msp [ T/T genotype compared with those carrying T/C and C/C genotypes.The individuals carrying CYP2D6c. 188 C/C or C/T genotype had a 1.23 times（95% CI ： 1.05 - 1.42, P = 0.01 ） increased risk compared with those carrying T/T genotypes. In no-smoking population, there was a 1.23 times（95% CI： 1.04 - 1.47, P = 0.01 ）increased risk of BP for subjects carrying CYP2D6c. 188 C/C or C/T genotypes compared with those carrying T/T genotype .The single nucleotide polymorphism of g. 212 position in the first extron of CYP2D6 gene had not been validated. Conclusion The individuals with CYP2D6 c. 188 C/C, CYP2D6 c. 188 C/T and CYPIAI Msp [ T/T genotypes tend to be more susceptible to benzene toxicity.