DNA修复基因多态性与二甲基甲酰胺致肝功能损伤关系的研究

目的研究DNA修复基因（XRCCl）的单核苷酸多态性与二甲基甲酰胺肝毒性易感性的关系。方法2010年9月至2011年7月，随机抽取福州市3家人造革生产企业，对PU革生产车间进行作业场所空气中二甲基甲酰胺浓度检测；对全部二甲基甲酰胺作业工人进行问卷调查和血丙氨酸氨基转氨酶（ALT）、天门冬氨酸氨基转氨酶（AST）、谷氨酰氨基转肽酶（GT）水平和XRCCl基因基因型检测。结果检测3家企业的9类二甲基甲酰胺作业工种的1lO个作业岗位，空气中二甲基甲酰胺浓度为（59．6±21．7）mg／m^2，有72个作业岗位超出职业接触限值（TWA20mg／m^2），超标率为65．45％。检测296名作业工人，肝功能异常（ALT≥50U／L、AST≥40U／L、GT≥54U／L中1项或1项以上）的78人，异常率为26．35％；xRCCl基因分为xRCCl—194CC组与CT＋TT组、xRCCl—280GG组与GA＋AA组，xRCCl-399GG组与GA＋AA组，各基因型的分布频率符合遗传学的Hardy—Weinberg平衡（P〉O．05）；不同基因型组（XRCCl—194的CC与CT＋TT、XRCCl—280的GG与GA＋AA、XRcCl399的GG与GA＋AA）工人血ALT、AST、GT水平的差异均无统计学意义（P〉0．05），肝功能异常率的差异均无统计学意义（P〉0．05）。结论XRCCl基因Argl94Trp、Arg280His、Arg399Gln多态性可能与二甲基甲酰胺肝毒性易感性无关。

Relationship Between Polymorphisms of Gene XRCC1 and Dimethylformamide-induced Liver Toxicity

Objective To explore the relationship between gene polymorphisms of XRCCl and susceptibility to dime thylformamide-induced liver toxicity. Methods Dimethylformamide consistency was detected from PU leather work- place in 3 tanneries,Fuzhou city, during September, 2010-July, 2011. All dimethylformamide-exposed workers were taken for questionnaire survey,and ALT, AST,GT levels in blood and XRCC1 genotype were analyzed. Results Dimethyl- formamide consistency was 59.6±21.7 mg/m^2 in 110 posts of 9 types of dimethylformamide work categories in 3 tanner ies. Dimethylformamide consistency in 72 posts exceeded the occupational exposure limit （TWA 20 mg/ma） ,and the over proofrate was 65.45%. There were 78 workers suffering from high liver function lever （ALT≥50 IU/L or ASTT≥40 IU/ L orGT≥54 IU/L） in 296 dimethylformamide-exposed workers, the incidence rate was 26.35~. The distribution fre quencies of alleles and genotypes of XRCC1 in 296 dimethylformamide-exposed workers accorded with Hardy-Weinberg e- quilibrium （ P 〉0.05）, the differences of blood ALT, AST, GT levels among different genetypes （XRCC1 194CC/CT ＋ TT,XRCC1-280GG/GA q- AA, XRCC1-399GG/GA ＋ AA） showed no statistical significance （ P 〉 0.05 ）, and the inci- dence rate of high liver function lever between the groups above-mentioned respectively had no statistical significance. Conclusion The XRCC1Arg194Trp, Arg280His, Arg399Gln polymorphisms are probably not the susceptible factors to dimethylformamide-induced liver toxicity.