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目的研究片状核酸内切酶1(flap endonuclease 1,Fen1)基因多态性与多环芳烃(polycyclic aromatic hydrocarbons,PAHs)接触工人外周血淋巴细胞DNA损伤易感性的相关性。方法选取137名焦炉作业工人(接触组)和49名无职业性PAHs及射线接触的医务人员(对照组)作为调查对象。测定尿中1-羟基芘(urinary 1-hydroxypyrene,1-OHPyr)水平反映PAHs接触内剂量,用碱性彗星试验评价个体外周血淋巴细胞DNA损伤,采用聚合酶链反应-限制性片段长度多态性方法分析Fen1基因rs4246215和rs174538位点的多态性。结果在校正性别、年龄、每日吸烟量、焦炉作业工龄和尿1-OHPyr后,接触组Fen1基因rs4246215、rs174538位点多态性与彗星Olive尾矩的关联差异有统计学意义(P<0.05),其中,携带杂合子基因型的个体彗星Olive尾矩短于携带突变型纯合子的个体,差异有统计学意义(P<0.05);携带不同单体型的个体彗星Olive尾矩,差异有统计学意义(P<0.05),其中携带GG/TA+TG单体型对的个体彗星Olive尾矩短于携带TA/TA+TG单体型对的个体,差异有统计学意义(P<0.01)。非暴露组Fen1基因rs4246215、rs174538位点多态性和不同单体型与彗星Olive尾矩的关联无统计学意义(P>0.05)。结论 Fen1基因rs4246215、rs174538位点的多态性可能是影响PAHs接触工人外周血淋巴细胞DNA损伤水平的易感性因素之一。
Objective To investigate the relationship between polymorphism of flap endonuclease 1 (Fen1) gene and susceptibility to DNA damage in workers’ peripheral blood lymphocytes exposed to polycyclic aromatic hydrocarbons (PAHs). Methods Totally 137 coke oven workers (contact group) and 49 non-occupational PAHs and radiographic medical staff (control group) were selected as the survey subjects. The level of urinary 1-hydroxypyrene (1-OHPyr) in the urine was measured to reflect the exposure dose of PAHs. DNA damage of peripheral blood lymphocytes was evaluated by alkaline comet assay. Polymerase chain reaction-restriction fragment length polymorphism Sex analysis of Fen1 gene rs4246215 and rs174538 polymorphisms. Results After correlating sex, age, daily smoking, coke oven working hours and urinary 1-OHPyr, there was a significant difference in the association between Fen1 gene rs4246215 and rs174538 polymorphism and Comet Olive tail moment (P < 0.05). Olive tail moments of comets carrying heterozygous genotypes were shorter than those carrying mutant homozygotes (P <0.05). Olive tail moments of comets carrying different haplotypes were significantly different (P <0.05). The Olive tails of individuals carrying GG / TA + TG haplotype were shorter than those carrying TA / TA + TG haplotype (P <0.05), the difference was statistically significant (P < 0.01). There were no significant differences in rs4246215 and rs174538 polymorphisms and different haplotypes in Olive tail between the non exposed group and Fenl gene (P> 0.05). Conclusion The polymorphism of rs4246215 and rs174538 in Fen1 gene may be one of the susceptible factors affecting the DNA damage level of PAHs exposed to peripheral blood lymphocytes in workers.