多环芳烃接触工人外周血全基因组DNA端粒长度与代谢相关基因多态性的关系

Association between polymorphisms of metabolic genes and teiomere length in workers exposed to polycyclic aromatic hydrocarbon

目的探讨多环芳烃（polycyclic aromatic hydrocarbons，PAHs）接触工人外周血全基因组DNA的端粒长度与PAHs代谢相关基因多态性的关系。方法选取145名焦炉作业工人（接触组）和68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（1-hydroxypyrene，1-OHP）水平反映PAHs接触内剂量，采用实时定量PCR的方法，测定研究对象外周血全基因组DNA的相对端粒长度（RTL），采用基于PCR的方法进行PAHs代谢相关基因多态性分析。结果与对照组（1．43±1．06）相比，PAHs接触组的RTL（1．10±0．75）明显缩短，差异有统计学意义（P=0．026）。校正了性别、年龄、每FI吸烟量和尿中1-OHP后，接触组CYPIAI基因3801T〉C位点CT基因型个体RTL（1．25±0．93）长于TT基因型（0．93±0．51），差异有统计学意义（P=0．043）；mEH基因Tyr^113His位点Tyr／His基因型个体RTL（0．90＋0．58）短于巩r／斯基因型（1．24±0．90），差异有统计学意义（P=0．043）；AHR基因rs10250822位点CT基因型个体RTL（1．02±0．64）短于CC基因型个体（1．36±1．14），差异有统计学意义（P=0．044）；AHR基因rs10247158位点AT基因型个体RTL（0．93±0．54）短于AA基因型（1．19±0．84），差异有统计学意义（P=0．047）。结论接触PAHs可以引起接触工人外周血全基因组DNARTL缩短，在PAHs接触丁人中，CYP1A1、mEH、AHR基因多态性可能是影响外周血全基因组DNARTL的遗传因素之一。

Objective To investigate the association between the polymorphisms of metabolic genes and telomere length of genomic DNA in peripheral blood of workers exposed to polyeyclic aromatic hydrocarbons （PAHs）. Methods One hundred and forty five coke-oven workers exposed to PAHs and sixty eight non-exposed medical staffs were recnfited in this study. Urinary 1-hydroxypyrene （1-OHP） served as the internal exposure dose of PAHs for all subjects. Relative telomere length （RTL） of genomic DNA in peripheral blood was used as telomere length and measured by real-time PCR. Polymorphisms of metabolic genes were detected by PCR-based methods. Results Compared with control group, the exposure group shown a decreased RTL （1.10±0.75 vs 1.43±1.06, P〈0.05）. In the coke-oven workers, after adjusting the sex, age, cigarettes per day and urinary 1-OHP, RTL （ 1.25±0.93 ） of workers with CT genotype at the CYP1A1 3801 T〉C was significantly longer than that （0.93±0.51 ） of workers with TT genotype （P〈0.05）. RTL （0.90±0.58） of individuals with the Tyr/His genotype at mEH Tyr113His was significantly shorter than that （1.24±0.90） of individuals with the Tyr/Tyr genotype （P〈0.05）. RTL （ 1.02±0.64 ） of individuals with the CT genotype at AHR rs 10250822 was significantly shorter than that （ 1.36± 1.14 ） of individuals with the CC genotype （P〈0.05）. RTL （0.93±0.54） of individuals with the AT genotype at AHR rs 10247158 was significantly shorter than that （ 1.19± 0.84） of individuals with the AA genotype （P〈0.05）. Conclusion The results of present study suggested that PAHs exposure could induce the shorted RTL, CYP1A1, mEH, AHR polymorphisms might influence the change of telomere length of genomic DNA in peripheral blood of workers exposed to PAHs.