【摘要】目的探讨尼古丁乙酰胆碱受体的CHRNA3-CHRNB4一CHRNA5基因簇多态性与焦炉TDNA损伤的联系。方法选择中国北方某焦化厂的309名工人作为研究对象,按照血浆中苯并(a)芘二氢二醇环氧化物(BPDE)一自蛋白加合物水平,将研究对象分为高暴露组(154人)和低暴露组(155人),使用健康体检调查表收集个人健康信息,采用碱性单细胞凝胶电泳技术评价淋巴细胞DNA损伤,基质辅助激光解吸电离飞行时间质谱技术检测基因多态性,使用Phasev2.1.1软件计算单体型对。结果高浓度多环芳烃暴露组T人外周血淋巴细胞彗星尾矩(OTM)值为1.23±1.05,低暴露组OTM值为O.80±1.07,两组比较,差异有统计学意义(P〈O.01)。在高暴露组中,CHRNA3-CHRNB4-CHRNA5基因簇的rs667282CC基因型携带者外周血淋巴细胞的OTM值(1.64±0.17)明显高于CT和CT+TT基因型携带者(0.95±0.13和1.09±0.11),差异有统计学意义(P〈0.01);rsl2910984GG基因型携带者外周血淋巴细胞的OTM值(1.60±0.17)明显高于AG和AG+AA基因型携带者(0.92±0.13和1.07±0.10),差异有统计学意义(P〈O.01)。单体型对的分析结果显示,在高暴露组中,人群巾分布最广的TA/CG单体型对携带者OTM值最低(0.89±0.13),TA/TA和CG/CG单体型对携带者OTM值分别为1.35±0.17和1.64±0.17,TA厂11A和CG/CG单体型对携带者的OTM值明显高于TA/CG单体型对携带者,差异有统计学意义(P〈0.05)。在低暴露组中,没有发现该基因簇多态性与DNA损伤之间的关联。结论CHRNA3一CHRNB4一CHRNA5基因簇多态性与焦炉工DNA损伤程度有关联。暴露于高浓度多环芳烃时,携带rs667282位点CC基[大j型的个体DNA损伤程度较其他基因型携带者高;携带rsl2910984位点GG基冈型的个体DNA损伤程度较其他基因型携带者高。为进一步阐明CHRNA3
Objective To investigate the relevance between single nueleotide polymorphisms (SNPs) in CHRNA3-CHRNB4-CHRNA5 gene cluster and DNA damage levels in the coke oven workers. Methods A total of 309 male subjects from a steel plant in Northern China were divided into high exposure group (154 workers) and low exposure group ( 155 workers) according to the concentrations of plasma benzoapyrene-r-7, t- 8, t-9, c-10-tetrahydotetrol-albumin (BPDE-AIb) adducts. DNA damage levels of peripheral blood lymphocytes were examined by comet assay. Allelie discrimination of SNPs in CHRNA3-CHRNB4-CHRNA5 gene cluster were detected using Matrix-assisted laser desorption/ionization mass spectrometry. Results The Olive tail mo- ment (OTM) (1.23±1.05) of peripheral blood lymphocytes in the high exposure group was significat~tly higher than that (0.80±1.07) in the low exposure group (P〈0.01). In the high exposure group, OTM (1.64±0.17) of subjects with rs667282CC genotype was significantly higher than those (0.95±0.13 or 1.09±0.11) of subjects with rs667282CT genotype or rs667282TT+CT genotype (P〈0.01); OTM (1.600.17) of subjects with GG geno- type at rs12910984 site was significantly higher than those (0.92±0.13 or 1.07±0.10) of subjects with AG genotype or AG+AA genotype (P〈O.01); OTM (1.35±0.17 or 1.64±0.17) of the TA/TA or CG/CG diplotype carriers was significantly higher than that (0.89_+0.13) of TA/CG diplotype carriers (P〈0.05). However, the rele-vance between genotypes of these SNPs and the DNA damage levels was not found in the low exposure group. Conclusion The rs667282CC genotype and rs12910984GG genotype on CHRNA3-CHRNB4-CHRNA5 gene cluster are associated with increased DNA damage levels in the high PAHs exposure group.